Engineering Papers⌕ Search

SEARCH · Engineering Papers

Results for “conformation dynamics”

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 433 records · Page 24
All sourcesNASA NTRSDOE OSTI
NASA NTRS1999

En route Spacing Tool: Efficient Conflict-free Spacing to Flow-Restricted Airspace

This paper describes the Air Traffic Management (ATM) problem within the U.S. of flow-restricted en route airspace, an assessment of its impact on airspace users, and a set of near-term tools and procedures to resolve the problem. The FAA is committed, over the next few years, to deploy the first generation of modem ATM decision support tool (DST) technology under the Free-Flight Phase-1 (FFp1) program. The associated en route tools include the User Request Evaluation Tool (URET) and the Traffic Management Advisor (TMA). URET is an initial conflict probe (ICP) capability that assists controllers with the detection and resolution of conflicts in en route airspace. TMA orchestrates arrivals transitioning into high-density terminal airspace by providing controllers with scheduled times of arrival (STA) and delay feedback advisories to assist with STA conformance. However, these FFPl capabilities do not mitigate the en route Miles-In-Trail (MIT) restrictions that are dynamically applied to mitigate airspace congestion. National statistics indicate that en route facilities (Centers) apply Miles-In-Trail (MIT) restrictions for approximately 5000 hours per month. Based on results from this study, an estimated 45,000 flights are impacted by these restrictions each month. Current-day practices for implementing these restrictions result in additional controller workload and an economic impact of which the fuel penalty alone may approach several hundred dollars per flight. To mitigate much of the impact of these restrictions on users and controller workload, a DST and procedures are presented. The DST is based on a simple derivative of FFP1 technology that is designed to introduce a set of simple tools for flow-rate (spacing) conformance and integrate them with conflict-probe capabilities. The tool and associated algorithms are described based on a concept prototype implemented within the CTAS baseline in 1995. A traffic scenario is used to illustrate the controller's use of the tool, and potential display options are presented for future controller evaluation.

Green, S.↗
DOE OSTI2025

Insights into distorted lamellar phases with small-angle scattering and machine learning

Lamellar phases are essential in various soft matter systems, with topological defects significantly influencing their mechanical properties. In this report, we present a machine-learning approach for quantitatively analyzing the structure and dynamics of distorted lamellar phases using scattering techniques. By leveraging the mathematical framework of Kolmogorov–Arnold networks, we demonstrate that the conformations of these distorted phases – expressed as superpositions of complex waves – can be reconstructed from small-angle scattering intensities. Through the contour analysis of wave field phase singularities, we obtain the statistics of the spatial distribution of topological defects. Furthermore, we establish that the temporal evolution of these defects can be derived from the time-dependent traveling wave field, informed by the dispersion relation of spectral components. This method opens new avenues for investigating the dynamics of distorted lamellar phases using various dynamic scattering techniques such as neutron spin echo and X-ray photon correlation spectroscopy. These findings enhance our microscopic understanding of how defects influence the physical properties of lamellar materials, with implications for both equilibrium and non-equilibrium states in general lamellar systems.

36 MATERIALS SCIENCE↗
DOE OSTI2023

Self-inhibited State of Venezuelan Equine Encephalitis Virus (VEEV) nsP2 Cysteine Protease: A Crystallographic and Molecular Dynamics Analysis

The Venezuelan equine encephalitis virus (VEEV) belongs to the Togaviridae family and is pathogenic to both humans and equines. The VEEV non-structural protein 2 (nsP2) is a cysteine protease (nsP2pro) that processes the polyprotein and thus it is a drug target for inhibitor discovery. The atomic structure of the VEEV nsP2 catalytic domain was previously characterized by both X-ray crystallography and computational studies. A modified nsP2pro harboring a N475A mutation in the N terminus was observed to exhibit an unexpected conformation: the N-terminal residues bind to the active site, mimicking binding of a substrate. The large conformational change of the N terminus was assumed to be induced by the N475A mutation, as N475 has an important role in stabilization of the N terminus and the active site. This conformation was first observed in the N475A mutant, but we also found it while determining a crystal structure of the catalytically active nsP2pro containing the wild-type N475 active site residue and K741A/K767A surface entropy reduction mutations. This suggests that the N475A mutation is not a prerequisite for self-inhibition. Here, we describe a high resolution (1.46 Å) crystal structure of a truncated nsP2pro (residues 463–785, K741A/K767A) and analyze the structure further by molecular dynamics to study the active and self-inhibited conformations of nsP2pro and its N475A mutant. A comparison of the different conformations of the N-terminal residues sheds a light on the interactions that play an important role in the stabilization of the enzyme.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Advances for QCD and the standard model: color-confining light-front holography and the principle of maximum conformality

Here, I review how the application of superconformal quantum mechanics and light-front holography leads to new insights into the physics of color confinement, the spectroscopy and dynamics of hadrons, as well as surprising supersymmetric relations between the masses of mesons, baryons, and tetraquarks. Spontaneous chiral symmetry breaking is automatically fulfilled by supersymmetric Light-Front QCD. The light-front holographic approach (HLFQCD) also predicts the behavior of the QCD running coupling and other observables from the nonperturbative color-confining domain to the perturbative domain. One can determine the QCD running coupling to high precision from the data of just a single experiment over the entire perturbative regime by using the Principle of Maximum Conformality (PMC). The PMC, which generalizes the conventional Gell-Mann-Low method for scale-setting in perturbative QED to non-Abelian QCD, provides a rigorous method for achieving unambiguous scheme-independent, fixed-order Standard Model predictions, consistent with the principles of the renormalization group. I also briefly review a novel feature of hadronic physics predicted by QCD: intrinsic heavy quarks.

Brodsky, Stanley J. [SLAC National Accelerator Lab↗
DOE OSTI2021

Fluorescent toxins as ion channel activity sensors.

Voltage gated ion channels (VGICs) shape the electrical character of cells by undergoing structural changes in response to membrane depolarization. High-resolution techniques have provided a wealth of data on individual VGIC structures, but the conformational changes of endogenous channels in live cell membranes have remained unexplored. Here, we describe methods for imaging structural changes of voltage-gated K + channels in living cells, using peptidyl toxins labeled with fluorophores that report specific protein conformations. These Endogenous Voltage-sensor Activity Probes (EVAPs) enable study of both VGIC allostery and function in the context of endogenous live-cell membranes under different physiological states. In this chapter, we describe methods for the synthesis, imaging, and analysis of dynamic EVAPs, which can report K + channel activity in complex tissue preparations via 2-photon excitation microscopy, and environment-sensitive EVAPs, which report voltage-dependent conformational changes at the VGIC-toxin interface. The methods here present the utility of current EVAPs and lay the groundwork for the development of other probes that act by similar mechanisms. EVAPs can be correlated with electrophysiology, offering insight into the molecular details of endogenous channel function and allostery in live cells. This enables investigation of conformational changes of channels in their native, functional states, putting structures and models into a context of live-cell membranes. The expansive array of state-dependent ligands and optical probes should enable probes more generally for investigating the molecular motions of endogenous proteins.

Stewart, Robert↗
DOE OSTI2025

Acetylcholinesterase: Structure, dynamics, and interactions with organophosphorus compounds

Acetylcholinesterase (AChE) is an enzyme that hydrolyzes the neurotransmitter acetylcholine (ACh), removing it from the synaptic cleft after the transmission of an electrical signal, making it an essential component of chemical neurotransmission. AChE is a serine hydrolase, containing a catalytic triad of Ser/His/Glu. AChE is a prime target for pharmaceuticals treating a variety of neurological disorders. It is also the target of synthetic organophosphorus (OP) compounds that have been used as pesticides and chemical warfare agents. OP compounds contain a potent leaving group, such as fluorine, and act by forming a covalent adduct with the catalytic serine of the AChE active site. A wealth of structural information is available for AChE, including over 300 structures, including a subset of structures in complex with drugs as well as OP compounds. This review will highlight the interactions between OP compounds and AChE from a structural and computational perspective, with a discussion of access to the active site, as well as side reactions that lead to dealkylation of the OP-catalytic serine adduct, a process known as aging. We conclude that while the majority of the conformational changes needed to accommodate the OP compounds are localized to the acyl loop in the crystal structures, molecular dynamics simulations highlight the potential for a far more dynamic enzyme.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS2004

Parallel 3D Mortar Element Method for Adaptive Nonconforming Meshes

High order methods are frequently used in computational simulation for their high accuracy. An efficient way to avoid unnecessary computation in smooth regions of the solution is to use adaptive meshes which employ fine grids only in areas where they are needed. Nonconforming spectral elements allow the grid to be flexibly adjusted to satisfy the computational accuracy requirements. The method is suitable for computational simulations of unsteady problems with very disparate length scales or unsteady moving features, such as heat transfer, fluid dynamics or flame combustion. In this work, we select the Mark Element Method (MEM) to handle the non-conforming interfaces between elements. A new technique is introduced to efficiently implement MEM in 3-D nonconforming meshes. By introducing an "intermediate mortar", the proposed method decomposes the projection between 3-D elements and mortars into two steps. In each step, projection matrices derived in 2-D are used. The two-step method avoids explicitly forming/deriving large projection matrices for 3-D meshes, and also helps to simplify the implementation. This new technique can be used for both h- and p-type adaptation. This method is applied to an unsteady 3-D moving heat source problem. With our new MEM implementation, mesh adaptation is able to efficiently refine the grid near the heat source and coarsen the grid once the heat source passes. The savings in computational work resulting from the dynamic mesh adaptation is demonstrated by the reduction of the the number of elements used and CPU time spent. MEM and mesh adaptation, respectively, bring irregularity and dynamics to the computer memory access pattern. Hence, they provide a good way to gauge the performance of computer systems when running scientific applications whose memory access patterns are irregular and unpredictable. We select a 3-D moving heat source problem as the Unstructured Adaptive (UA) grid benchmark, a new component of the NAS Parallel Benchmarks (NPB). In this paper, we present some interesting performance results of ow OpenMP parallel implementation on different architectures such as the SGI Origin2000, SGI Altix, and Cray MTA-2.

Feng, Huiyu↗
DOE OSTI2020

Transient Unfolding and Long-Range Interactions in Viral BCL2 M11 Enable Binding to the BECN1 BH3 Domain

Viral BCL2 proteins (vBCL2s) help to sustain chronic infection of host proteins to inhibit apoptosis and autophagy. However, details of conformational changes in vBCL2s that enable binding to BH3Ds remain unknown. Using all-atom, multiple microsecond-long molecular dynamic simulations (totaling 17 μs) of the murine γ-herpesvirus 68 vBCL2 (M11), and statistical inference techniques, we show that regions of M11 transiently unfold and refold upon binding of the BH3D. Further, we show that this partial unfolding/refolding within M11 is mediated by a network of hydrophobic interactions, which includes residues that are 10 Å away from the BH3D binding cleft. We experimentally validate the role of these hydrophobic interactions by quantifying the impact of mutating these residues on binding to the Beclin1/BECN1 BH3D, demonstrating that these mutations adversely affect both protein stability and binding. To our knowledge, this is the first study detailing the binding-associated conformational changes and presence of long-range interactions within vBCL2s.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Dual arginine recognition of LRRK2 phosphorylated Rab GTPases

Parkinson’s-disease-associated LRRK2 is a multidomain Ser/Thr kinase that phosphorylates a subset of Rab GTPases to control their effector functions. Rab GTPases are the prime regulators of membrane trafficking in eukaryotic cells. Rabs exert their biological effects by recruitment of effector proteins to subcellular compartments via their Rab-binding domain (RBD). Effectors are modular and typically contain additional domains that regulate various aspects of vesicle formation, trafficking, fusion, and organelle dynamics. The RBD of effectors is typically an α-helical coiled coil that recognizes the GTP conformation of the switch 1 and switch 2 motifs of Rabs. LRRK2 phosphorylates Rab8a at T72 (pT72) of its switch 2 α-helix. This post-translational modification enables recruitment of RILPL2, an effector that regulates ciliogenesis in model cell lines. A newly identified RBD motif of RILPL2, termed the X-cap, has been shown to recognize the phosphate via direct interactions between an arginine residue (R132) and pT72 of Rab8a. Here, we show that a second distal arginine (R130) is also essential for phospho-Rab binding by RILPL2. Through structural, biophysical, and cellular studies, we find that R130 stabilizes the primary R132:pT72 salt bridge through favorable enthalpic contributions to the binding affinity. These findings may have implications for the mechanism by which LRRK2 activation leads to assembly of phospho-Rab complexes and subsequent control of their membrane trafficking functions in cells.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Molecular simulation of glycerol-derived triether podands for lithium ion solvation

Solvate ionic liquids (ILs) are promising candidates for several applications due to their stability, high coulombic efficiency, and low volatility. In this work, we investigate the solvation of lithium-bistriflimide by different glycerol-derived triether solvents, using molecular dynamics simulations. Very strong interactions between Li + and the solvent oxygen sites are found, leading to significant conformational changes in the solvent. Here, by comparing the conformation of the neat solvents with their IL mixtures at different concentrations and temperatures, we find that the presence of Li + induces a distinct crown-like structure in the solvent molecules. The Li + cations and the surrounding solvent form a podand complex, which is stable even at elevated temperatures. These glycerol-derived solvents exhibit distinct interactions with Li + cations which may be exploited in electrolytic applications or lithium recovery processes.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
NASA NTRS1980

Grid generation for two-dimensional finite element flowfield computation

The finite element method for fluid dynamics was used to develop a two dimensional mesh generation scheme. The method consists of shearing and conformal maps with upper and lower surfaces handled independently to allow sharp leading edges. The method also generates meshes of triangular or quadrilateral elements.

Tatum, K. E.↗
DOE OSTI2022

Conformational motions and ligand-binding underlying gating and regulation in IP 3 R channel

Inositol-1,4,5-trisphosphate receptors (IP3Rs) are activated by IP 3 and Ca 2+ and their gating is regulated by various intracellular messengers that finely tune the channel activity. Here, using single particle cryo-EM analysis we determined 3D structures of the nanodisc-reconstituted IP 3 R1 channel in two ligand-bound states. These structures provide unprecedented details governing binding of IP 3 , Ca 2+ and ATP, revealing conformational changes that couple ligand-binding to channel opening. Using a deep-learning approach and 3D variability analysis we extracted molecular motions of the key protein domains from cryo-EM density data. We find that IP 3 binding relies upon intrinsic flexibility of the ARM2 domain in the tetrameric channel. Our results highlight a key role of dynamic side chains in regulating gating behavior of IP 3 R channels. This work represents a stepping-stone to developing mechanistic understanding of conformational pathways underlying ligand-binding, activation and regulation of the channel.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Structure of the Diphtheria Toxin at Acidic pH: Implications for the Conformational Switching of the Translocation Domain

Diphtheria toxin, an exotoxin secreted by Corynebacterium that causes disease in humans by inhibiting protein synthesis, enters the cell via receptor-mediated endocytosis. The subsequent endosomal acidification triggers a series of conformational changes, resulting in the refolding and membrane insertion of the translocation (T-)domain and ultimately leading to the translocation of the catalytic domain into the cytoplasm. Here, we use X-ray crystallography along with circular dichroism and fluorescence spectroscopy to gain insight into the mechanism of the early stages of pH-dependent conformational transition. For the first time, we present the high-resolution structure of the diphtheria toxin at a mildly acidic pH (5–6) and compare it to the structure at neutral pH (7). We demonstrate that neither catalytic nor receptor-binding domains change their structure upon this acidification, while the T-domain undergoes a conformational change that results in the unfolding of the TH2–3 helices. Surprisingly, the TH1 helix maintains its conformation in the crystal of the full-length toxin even at pH 5. This contrasts with the evidence from the new and previously published data, obtained by spectroscopic measurements and molecular dynamics computer simulations, which indicate the refolding of TH1 upon the acidification of the isolated T-domain. The overall results imply that the membrane interactions of the T-domain are critical in ensuring the proper conformational changes required for the preparation of the diphtheria toxin for the cellular entry.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Arbitrary Order Virtual Element Methods for High‐Order Phase‐Field Modeling of Dynamic Fracture

ABSTRACT Accurate modeling of fracture nucleation and propagation in brittle and ductile materials subjected to dynamic loading is important in predicting material damage and failure under extreme conditions. Phase‐field fracture models have garnered a lot of attention in recent years due to their success in representing damage and fracture processes in a wide class of materials and under a variety of loading conditions. Second‐order phase‐field fracture models are by far the most popular among researchers (and increasingly, among practitioners), but fourth‐order models have started to gain broader acceptance since their more recent introduction. The exact solution corresponding to these high‐order phase‐field fracture models has higher regularity. Thus, numerical solutions of the model equations can achieve improved accuracy and higher spatial convergence rates. In this work, we develop a virtual element framework for the high‐order phase‐field model of dynamic fracture. The virtual element method (VEM) can be regarded as a generalization of the classical finite element method. In addition to many other desirable characteristics, the VEM allows computing on polytopal meshes. Here, we use ‐conforming virtual elements and the generalized‐ time integration method for the momentum balance equation, and adopt ‐conforming virtual elements for the high‐order phase‐field equation. We verify our virtual element framework using classical quasi‐static benchmark problems and demonstrate its capabilities with the aid of numerical simulations of dynamic fracture in brittle materials.

42 ENGINEERING↗
NASA NTRS1989

Dynamic grid deformation using Navier-displacement equation for deforming wings

For dynamic and aeroelastic applications of maneuvering wings, the solid boundaries undergo rigid-body motion and aeroelastic deformation. For rigid-body motion, the conservative fluid dynamics equation, in terms of the Eulerian description, is written in terms of a moving frame of reference, and the problem is solved on a time-independent body-conformed grid. For both rigid-body motion and aeroelastic deformation, the Navier-displacement equation, in terms of the Lagrangian coordinates, is modified for fluid-flow problems. It is used along with the Eulerian description of the conservative fluid dynamics equations to account for the grid deformation.

Kandil, Osama A.↗
DOE OSTI2020

SNS: A Solution-Based Nonlinear Subspace Method for Time-Dependent Model Order Reduction

Several reduced order models have been successfully developed for nonlinear dynamical systems. To achieve a considerable speed-up, a hyper-reduction step is needed to reduce the computational complexity due to nonlinear terms. Many hyper-reduction techniques require the construction of nonlinear term basis, which introduces a computationally expensive offline phase. A novel way of constructing nonlinear term basis within the hyper-reduction process is introduced. In contrast to the traditional hyper-reduction techniques where the collection of nonlinear term snapshots is required, the SNS method avoids collecting the nonlinear term snapshots. Instead, it uses the solution snapshots that are used for building a solution basis, which enables avoiding an extra data compression of nonlinear term snapshots. As a result, the SNS method provides a more efficient offline strategy than the traditional model order reduction techniques, such as the DEIM, GNAT, and ST-GNAT methods. The SNS method is theoretically justified by the conforming subspace condition and the subspace inclusion relation. It is useful for model order reduction of large-scale nonlinear dynamical problems to reduce the offline cost. It is especially useful for ST-GNAT that has shown promising results, such as a good accuracy with a considerable online speed-up for hyperbolic problems in a recent paper by Choi and Carlberg [SIAM J. Sci. Comput., 41 (2019), pp. A26--A58], because ST-GNAT involves an expensive offline cost related to collecting nonlinear term snapshots. Error analysis for the SNS method is presented. Numerical results support that the accuracy of the solution from the SNS method is comparable to the traditional methods and a considerable speed-up (i.e., a factor of two to a hundred) is achieved in the offline phase.

97 MATHEMATICS AND COMPUTING↗
DOE OSTI2024

Structural basis of transcription: RNA polymerase II substrate binding and metal coordination using a free-electron laser

Catalysis and translocation of multisubunit DNA-directed RNA polymerases underlie all cellular mRNA synthesis. RNA polymerase II (Pol II) synthesizes eukaryotic pre-mRNAs from a DNA template strand buried in its active site. Structural details of catalysis at near-atomic resolution and precise arrangement of key active site components have been elusive. Here, we present the free-electron laser (FEL) structures of a matched ATP-bound Pol II and the hyperactive Rpb1 T834P bridge helix (BH) mutant at the highest resolution to date. The radiation-damage-free FEL structures reveal the full active site interaction network, including the trigger loop (TL) in the closed conformation, bonafide occupancy of both site A and B Mg 2+ , and, more importantly, a putative third (site C) Mg 2+ analogous to that described for some DNA polymerases but not observed previously for cellular RNA polymerases. Molecular dynamics (MD) simulations of the structures indicate that the third Mg 2+ is coordinated and stabilized at its observed position. TL residues provide half of the substrate binding pocket while multiple TL/BH interactions induce conformational changes that could allow translocation upon substrate hydrolysis. Consistent with TL/BH communication, a FEL structure and MD simulations of the T834P mutant reveal rearrangement of some active site interactions supporting potential plasticity in active site function and long-distance effects on both the width of the central channel and TL conformation, likely underlying its increased elongation rate at the expense of fidelity.

Science & Technology - Other Topics↗
NASA NTRS1989

Unsteady aerodynamics methods for transonic aeroelastic analysis

The paper describes the current status of methods development for transonic aeroelastic analysis within the Unsteady Aerodynamics Branch at NASA Langley. The paper first highlights the development of an approximate factorization (AF) algorithm for solution of the unsteady transonic small-distribution (TSD) equation. The AF algorithm has been used as the basis for a three-dimensional TSD code for complete aircraft applications. The paper also describes the development of solution algorithms for the unsteady Euler equations based on the use of unstructured meshes. These Euler methods contain a dynamic mesh algorithm, which is a general procedure to move or deform the mesh so that it continuously conforms to the instantaneous shape of the aeroelastically deformed vehicle.

Batina, John T.↗