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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 37 records · Page 2
All sourcesNASA NTRSDOE OSTI
NASA NTRS2022

Evolution and folding of repeat proteins

Repeat proteins are made with tandem copies of similar amino acid stretches that fold into elongated architectures. These proteins constitute excellent model systems to investigate how evolution relates to structure, folding, and function. Here, we propose a scheme to map evolutionary information at the sequence level to a coarse-grained model for repeat-protein folding and use it to investigate the folding of thousands of repeat proteins. We model the energetics by a combination of an inverse Potts-model scheme with an explicit mechanistic model of duplications and deletions of repeats to calculate the evolutionary parameters of the system at the single-residue level. These parameters are used to inform an Ising-like model that allows for the generation of folding curves, apparent domain emergence, and occupation of intermediate states that are highly compatible with experimental data in specific case studies. We analyzed the folding of thousands of natural Ankyrin repeat proteins and found that a multiplicity of folding mechanisms are possible. Fully cooperative all-or-none transitions are obtained for arrays with enough sequence-similar elements and strong interactions between them, while noncooperative element-by-element intermittent folding arose if the elements are dissimilar and the interactions between them are energetically weak. Additionally, we characterized nucleation-propagation and multidomain folding mechanisms. We show that the global stability and cooperativity of the repeating arrays can be predicted from simple sequence scores.

Ezequiel A. Galpern↗
NASA NTRS1998

Folding and translocation of the undecamer of poly-L-leucine across the water-hexane interface. A molecular dynamics study

The undecamer of poly-L-leucine at the water-hexane interface is studied by molecular dynamics simulations. This represents a simple model relevant to folding and insertion of hydrophobic peptides into membranes. The peptide, initially placed in a random coil conformation on the aqueous side of the system, rapidly translocates toward the hexane phase and undergoes interfacial folding into an alpha-helix in the subsequent 36 ns. Folding is nonsequential and highly dynamic. The initially formed helical segment at the N-terminus of the undecamer becomes transiently broken and, subsequently, reforms before the remainder of the peptide folds from the C-terminus. The formation of intramolecular hydrogen bonds during the folding of the peptide is preceded by a dehydration of the participating polar groups, as they become immersed in hexane. Folding proceeds through a short-lived intermediate, a 3(10)-helix, which rapidly interconverts to an alpha-helix. Both helices contribute to the equilibrium ensemble of folded structures. The helical peptide is largely buried in hexane, yet remains adsorbed at the interface. Its preferred orientation is parallel to the interface, although the perpendicular arrangement with the N-terminus immersed in hexane is only slightly less favorable. In contrast, the reversed orientation is highly unfavorable, because it would require dehydration of C-terminus carbonyl groups that do not participate in intramolecular hydrogen bonding. For the same reason, the transfer of the undecamer from the interface to the bulk hexane is also unfavorable. The results suggest that hydrophobic peptides fold in the interfacial region and, simultaneously, translocate into the nonpolar side of the interface. It is further implied that peptide insertion into the membrane is accomplished by rotating from the parallel to the perpendicular orientation, most likely in such a way that the N-terminus penetrates the bilayer.

NASA Discipline Exobiology↗
DOE OSTI2021

Interplay of folded domains and the disordered low-complexity domain in mediating hnRNPA1 phase separation

Abstract Liquid–liquid phase separation underlies the membrane-less compartmentalization of cells. Intrinsically disordered low-complexity domains (LCDs) often mediate phase separation, but how their phase behavior is modulated by folded domains is incompletely understood. Here, we interrogate the interplay between folded and disordered domains of the RNA-binding protein hnRNPA1. The LCD of hnRNPA1 is sufficient for mediating phase separation in vitro. However, we show that the folded RRM domains and a folded solubility-tag modify the phase behavior, even in the absence of RNA. Notably, the presence of the folded domains reverses the salt dependence of the driving force for phase separation relative to the LCD alone. Small-angle X-ray scattering experiments and coarse-grained MD simulations show that the LCD interacts transiently with the RRMs and/or the solubility-tag in a salt-sensitive manner, providing a mechanistic explanation for the observed salt-dependent phase separation. These data point to two effects from the folded domains: (i) electrostatically-mediated interactions that compact hnRNPA1 and contribute to phase separation and (ii) increased solubility at higher ionic strengths mediated by the folded domains. The interplay between disordered and folded domains can modify the dependence of phase behavior on solution conditions and can obscure signatures of physicochemical interactions underlying phase separation.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Visualizing nucleation, condensation and propagation of β-tubulin folding in chaperonin TRiC

AbstractThe folding nucleus (FN) initiates protein folding and enables an efficient folding pathway. Here we directly visualize the tubulin FN consisting of a nonnative, partially assembled Rossmann fold, in the closed chamber of human chaperonin TRiC. Chaperonin TRiC interacts with non-natively folded secondary structural elements, stabilizing the nucleus for transition into its first native domain. Through progressive folding, the unfolded sequence goes through drastic spatial arrangement in the TRiC chamber to sample the conformational space, mediated by the highly dynamic CCT tails. The observed presence of individual nonnative secondary structures first in the nonnative FN and then around the incrementally folded native domains supports the hypothesis that tubulin folding in TRiC is a hierarchical process of nucleation, condensation and propagation in cooperation with TRiC subunits.

Zhao, Yanyan (ORCID:0000000323021763)↗
DOE OSTI2024

Mechanism of DNA origami folding elucidated by mesoscopic simulations

Abstract Many experimental and computational efforts have sought to understand DNA origami folding, but the time and length scales of this process pose significant challenges. Here, we present a mesoscopic model that uses a switchable force field to capture the behavior of single- and double-stranded DNA motifs and transitions between them, allowing us to simulate the folding of DNA origami up to several kilobases in size. Brownian dynamics simulations of small structures reveal a hierarchical folding process involving zipping into a partially folded precursor followed by crystallization into the final structure. We elucidate the effects of various design choices on folding order and kinetics. Larger structures are found to exhibit heterogeneous staple incorporation kinetics and frequent trapping in metastable states, as opposed to more accessible structures which exhibit first-order kinetics and virtually defect-free folding. This model opens an avenue to better understand and design DNA nanostructures for improved yield and folding performance.

77 NANOSCIENCE AND NANOTECHNOLOGY↗
NASA NTRS2014

Origami-Inspired Folding of Thick, Rigid Panels

To achieve power of 250 kW or greater, a large compression ratio of stowed-to-deployed area is needed. Origami folding patterns were used to inspire the folding of a solar array to achieve synchronous deployment; however, origami models are generally created for near-zero-thickness material. Panel thickness is one of the main challenges of origami-inspired design. Three origami-inspired folding techniques (flasher, square twist, and map fold) were created with rigid panels and hinges. Hinge components are added to the model to enable folding of thick, rigid materials. Origami models are created assuming zero (or near zero) thickness. When a material with finite thickness is used, the panels are required to bend around an increasingly thick fold as they move away from the center of the model. The two approaches for dealing with material thickness are to use membrane hinges to connect the panels, or to add panel hinges, or hinges of the same thickness, at an appropriate width to enable folding.

Trease, Brian P.↗
DOE OSTI2020

Quality-Control Mechanism for Telomerase RNA Folding in the Cell

Long non-coding RNAs can often fold into different conformations. Telomerase RNA, an essential component of the telomerase ribonucleoprotein (RNP) enzyme, must fold into a defined structure to fulfill its function with the protein catalytic subunit (TERT) and other accessory factors. However, the mechanism by which the correct folding of telomerase RNA is warranted in a cell is still unknown. Here we show that La-related protein Pof8 specifically recognizes the conserved pseudoknot region of telomerase RNA and instructs the binding of the Lsm2-8 complex to its mature 3' end, thus selectively protecting the correctly folded RNA from exonucleolytic degradation. In the absence of Pof8, TERT assembles with misfolded RNA and produces little telomerase activity. Therefore, Pof8 plays a key role in telomerase RNA folding quality control, ensuring that TERT only assembles with functional telomerase RNA to form active telomerase. Our finding reveals a mechanism for non-coding RNA folding quality control.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

SEC ‐ SAXS / MC Ensemble Structural Studies of the Microtubule Binding Protein Cdt1 Show Monomeric, Folded‐Over Conformations

ABSTRACT Cdt1 is a mixed folded protein critical for DNA replication licensing and it also has a “moonlighting” role at the kinetochore via direct binding to microtubules and the Ndc80 complex. However, it is unknown how the structure and conformations of Cdt1 could allow it to participate in these multiple, unique sets of protein complexes. While robust methods exist to study entirely folded or unfolded proteins, structure–function studies of combined, mixed folded/disordered proteins remain challenging. In this work, we employ orthogonal biophysical and computational techniques to provide structural characterization of mitosis‐competent human Cdt1. Thermal stability analyses shows that both folded winged helix domains1 are unstable. CD and NMR show that the N‐terminal and linker regions are intrinsically disordered. DLS shows that Cdt1 is monomeric and polydisperse, while SEC‐MALS confirms that it is monomeric at high concentrations, but without any apparent inter‐molecular self‐association. SEC‐SAXS enabled computational modeling of the protein structures. Using the program SASSIE, we performed rigid body Monte Carlo simulations to generate a conformational ensemble of structures. We observe that neither fully extended nor extremely compact Cdt1 conformations are consistent with SAXS. The best‐fit models have the N‐terminal and linker disordered regions extended into the solution and the two folded domains close to each other in apparent “folded over” conformations. We hypothesize the best‐fit Cdt1 conformations could be consistent with a function as a scaffold protein that may be sterically blocked without binding partners. Our study also provides a template for combining experimental and computational techniques to study mixed‐folded proteins.

Cell Biology↗
DOE OSTI2022

Novel fold of rotavirus glycan-binding domain predicted by AlphaFold2 and determined by X-ray crystallography

The VP8* domain of spike protein VP4 in group A and C rotaviruses, which cause epidemic gastroenteritis in children, exhibits a conserved galectin-like fold for recognizing glycans during cell entry. In group B rotavirus, which causes significant diarrheal outbreaks in adults, the VP8* domain (VP8*B) surprisingly lacks sequence similarity with VP8* of group A or group C rotavirus. Here, by using the recently developed AlphaFold2 for ab initio structure prediction and validating the predicted model by determining a 1.3-Å crystal structure, we show that VP8*B exhibits a novel fold distinct from the galectin fold. This fold with a β-sheet clasping an α-helix represents a new fold for glycan recognition based on glycan array screening, which shows that VP8*B recognizes glycans containing N-acetyllactosamine moiety. Although uncommon, our study illustrates how evolution can incorporate structurally distinct folds with similar functionality in a homologous protein within the same virus genus.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS1972

Life prediction of expulsion bladders through fatigue test and fold strain analysis.

Consideration of the problem of reducing the probability of mechanical failure of bladder systems used for the expulsion of propellants into liquid rocket engines. It is shown that individual local folds in collapsing bladders can be classified into single and double folds, specifiable by nondimensional geometrical parameters which directly define the maximum strains at these folds. From these maximum strains the number of collapse/inflation cycles to failure can be obtained from low-cycle fatigue data experimentally determined for the bladder material of interest. Cycle life data are presented in terms of true maximum strain for four metals, two plastics, and two elastomers. It is found that double folds give rise to much more severe folding strains than do simple folds.

Chu, H. N.↗
DOE OSTI2022

Folding Coarse-Grained Oligomer Models with PyRosetta

Non-biological foldamers are a promising class of macromolecules that share similarities to classical biopolymers such as proteins and nucleic acids. Currently, designing novel foldamers is a non-trivial process, often involving many iterations of trial synthesis and characterization until folded structures are observed. In this work, we aim to tackle these foldamer design challenges using computational modeling techniques. We developed CG PyRosetta, an extension to the popular protein folding python package, PyRosetta, which introduces coarse-grained (CG) residues into PyRosetta, enabling the folding of toy CG foldamer models. Although these models are simplified, they can help explore overarching physical hypotheses about how oligomers can form. Through systematic variation of CG parameters in these models, we can investigate various folding hypotheses at the CG scale to inform the design process of new foldamer chemistries. In this study, we demonstrate CG PyRosetta’s ability to identify minimum energy structures with a diverse structural search over a range of simple models, as well as two hypothesis-driven parameter scans investigating the effects of side-chain size and internal backbone angle on secondary structures. We are able to identify several types of secondary structures from single- and double-helices to sheet-like and knot-like structures. Here, we show how side-chain size and backbone bond angle both play an important role in the structure and energetics of these toy models. Optimal side-chain sizes promote favorable packing of side chains, while specific backbone bond angles influence the specific helix type found in folded structures.

36 MATERIALS SCIENCE↗
DOE OSTI2022

Electric-field control of the nucleation and motion of isolated three-fold polar vertices

Recently various topological polar structures have been discovered in oxide thin films. Despite the increasing evidence of their switchability under electrical and/or mechanical fields, the dynamic property of isolated ones, which is usually required for applications such as data storage, is still absent. Here, we show the controlled nucleation and motion of isolated three-fold vertices under an applied electric field. At the PbTiO 3 /SrRuO 3 interface, a two-unit-cell thick SrTiO 3 layer provides electrical boundary conditions for the formation of three-fold vertices. Utilizing the SrTiO 3 layer and in situ electrical testing system, we find that isolated three-fold vertices can move in a controllable and reversible manner with a velocity up to ~629 nm s -1 . Microstructural evolution of the nucleation and propagation of isolated three-fold vertices is further revealed by phase-field simulations. This work demonstrates the ability to electrically manipulate isolated three-fold vertices, shedding light on the dynamic property of isolated topological polar structures.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗
NASA NTRS1999

Observations of Convective and Dynamical Instabilities in Tropopause Folds and their Contribution to Stratosphere-Troposphere Exchange

With aircraft-mounted in-situ and remote sensing instruments for dynamical, thermal. and chemical measurements, we studied two cases of tropopause folding. In both folds we found Kelvin-Helmholtz billows with horizontal wavelength of about 900 m and thickness of about 120 m. In one case the instability was effectively mixing the bottomside of the fold, leading to the transfer of stratospheric air into the troposphere. Also we discovered in both cases small-scale secondary ozone maxima shortly after the aircraft ascended past the topside of the fold that corresponded to regions of convective instability. We interpreted this phenomenon as convectively breaking gravity waves. Therefore, we posit that convectively breaking gravity waves acting on tropopause folds must be added to the list of important irreversible mixing mechanisms leading to stratosphere-troposphere exchange.

Cho, John Y. N.↗
NASA NTRS1997

Molecular Dynamics of Peptide Folding at Aqueous Interfaces

Even though most monomeric peptides are disordered in water they can adopt sequence-dependent, ordered structures, such as a-helices, at aqueous interfaces. This property is relevant to cellular signaling, membrane fusion, and the action of toxins and antibiotics. The mechanism of folding nonpolar peptides at the water-hexane interface was studied in the example of an 11-mer, of poly-L-leucine. Initially placed as a random coil on the water side of the interface, the peptide folded into an a-helix in 36 ns. Simultaneously, the peptide translocated into the hexane side of the interface. Folding was not sequential and involved a 3/10-helix as an intermediate. The folded peptide was either parallel to the interface or had its C-terminus exposed to water. An 11-mer, LQQLLQQLLQL, composed of leucine (L) and glutamine (G), was taken as a model amphiphilic peptide. It rapidly adopted an amphiphilic, disordered structure at the interface. Further folding proceeded through a series of amphiphilic intermediates.

Pohorille, Andrew↗
DOE OSTI2025

Carbon Storage in Fold‐and‐Thrust Belts: An Overlooked Gigatonne Storage Opportunity

This study presents numerical investigations of the trapping characteristics of fold-and-thrust belt structures, defining three carbon capture and storage (CCS) play types that could be used to store commercial volumes (millions of tonnes) of CO 2 . Specifically, we present simulations of CO 2 storage in three fold-and-thrust belt models comprising a thrust-ramp, duplex, and thrust-fold geometry. To constrain these play types in realistic geology, each model is based on a study site, including a novel investigation of a greenfield saline reservoir in Virginia, USA, being considered for commercial carbon storage and two well-characterized petroleum fields: the Wilburton field in Oklahoma, USA, and the Incahuasi field in Bolivia. Our results provide insight into several key parameters, such as the long-term security of injected CO 2 in these geologies and injection strategies for maximizing storage efficiency while reducing pressure-related risk. These results improve the understanding of CCS in fold-and-thrust belt storage sites globally by describing general storage parameters that may be applied to site-specific projects. We find that thrust-ramp geometries may securely trap CO 2 through solubility and hydrodynamic trapping under suitable reservoir conditions, duplex structures may store some quantities of CO 2 but are pressure-constrained, and that thrust-ramp structures may store large quantities of CO 2 by maximizing fetch volume, which simultaneously lowers geomechanical risk by reducing pressure buildup along zones of weakness.

42 ENGINEERING↗
DOE OSTI2021

Atomistic Mechanics of Torn Back Folded Edges of Triangular Voids in Monolayer WS 2

Triangular nanovoids in 2D materials transition metal dichalcogenides have vertex points that cause stress concentration and lead to sharp crack propagation and failure. Here, the atomistic mechanics of back folding around triangular nanovoids in monolayer WS 2 sheets is examined. Combining atomic-resolution images from annular dark-field scanning transmission electron microscopy with reactive molecular modelling, it is revealed that the folding edge formation has statistical preferences under geometric conditions based on the orientation mismatch. It is further investigated how loading directions and strong interlayer friction, interplay with WS 2 lattice's crack preference, govern the deformation and fracture pattern around folding edges. Finally, these results provide fundamental insights into the combination of fracture and folding in flexible monolayer crystals and the resultant Moiré lattices.

36 MATERIALS SCIENCE↗
DOE OSTI2023

Structural and dynamic mechanisms for coupled folding and tRNA recognition of a translational T-box riboswitch

T-box riboswitches are unique riboregulators where gene regulation is mediated through interactions between two highly structured RNAs. Despite extensive structural insights, how RNA-RNA interactions drive the folding and structural transitions of T-box to achieve functional conformations remains unclear. Here, by combining SAXS, single-molecule FRET and computational modeling, we elaborate the folding energy landscape of a translational T-box aptamer consisting of stems I, II and IIA/B, which Mg 2+ -induced global folding and tRNA binding are cooperatively coupled. smFRET measurements reveal that high Mg 2+ stabilizes IIA/B and its stacking on II, which drives the pre-docking of I and II into a competent conformation, subsequent tRNA binding promotes docking of I and II to form a high-affinity tRNA binding groove, of which the essentiality of IIA/B and S-turn in II is substantiated with mutational analysis. We highlight a delicate balance among Mg 2+ , the intra- and intermolecular RNA-RNA interactions in modulating RNA folding and function.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Structural basis of tRNA recognition by the widespread OB fold

The widespread oligonucleotide/oligosaccharide-binding (OB)-fold recognizes diverse substrates from sugars to nucleic acids and proteins, and plays key roles in genome maintenance, transcription, translation, and tRNA metabolism. OB-containing bacterial Trbp and yeast Arc1p proteins are thought to recognize the tRNA elbow or anticodon regions. Here we report a 2.6 Å co-crystal structure of Aquifex aeolicus Trbp111 bound to tRNA Ile , which reveals that Trbp recognizes tRNAs solely by capturing their 3' ends. Structural, mutational, and biophysical analyses show that the Trbp/EMAPII-like OB fold precisely recognizes the single-stranded structure, 3' terminal location, and specific sequence of the 3' CA dinucleotide — a universal feature of mature tRNAs. Arc1p supplements its OB – tRNA 3' end interaction with additional contacts that involve an adjacent basic region and the tRNA body. This study uncovers a previously unrecognized mode of tRNA recognition by an ancient protein fold, and provides insights into protein-mediated tRNA aminoacylation, folding, localization, trafficking, and piracy.

59 BASIC BIOLOGICAL SCIENCES↗