Engineering Papers⌕ Search

SEARCH · Engineering Papers

Results for “Molecular conformation”

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 145 records · Page 8
All sourcesNASA NTRSDOE OSTI
DOE OSTI2024

Unified understanding of the impact of semiflexibility, concentration, and molecular weight on macromolecular-scale ring diffusion

Conformationally fluctuating, globally compact macromolecules such as polymeric rings, single-chain nanoparticles, microgels, and many-arm stars display complex dynamic behaviors due to their rich topological structure and intermolecular organization. Synthetic rings are hybrid objects with conformations that display both ideal random walk and compact globular features, which can serve as models of genomic DNA. To date, emphasis has been placed on the effect of ring molecular weight on their unusual behaviors. Here, we combine simulations and a microscopic force-level theory to build a unified understanding for how key aspects of ring dynamics depend on different tunable molecular properties including backbone rigidity, monomer concentration, degree of traditional entanglement, and molecular weight. Our large-scale molecular dynamics simulations of ring melts with very different backbone stiffnesses reveal unanticipated behaviors which agree well with our generalized theory. This includes a universal master curve for center-of-mass diffusion constants as a function of molecular weight scaled by a chemistry and thermodynamic state-dependent critical molecular weight that generalizes the concept of an entanglement cross-over for linear chains. The key physics is how backbone rigidity and monomer concentration induced changes of the entanglement length, interring packing, degree of interpenetration, and liquid compressibility slow down space-time dynamic-force correlations on macromolecular scales. A power law decay of the center-of-mass diffusion constant with inverse molecular weight squared is the first consequence, followed by an ultraslow activated hopping transport regime. Our results set the stage to address slow dynamics and kinetic arrest in different families of compact synthetic and biological polymeric systems.

Science & Technology - Other Topics↗
DOE OSTI2022

Structure of maize BZR1-type β-amylase BAM8 provides new insights into its noncatalytic adaptation

Plant β-amylase (BAM) proteins play an essential role in growth, development, stress response, and hormone regulation. Despite their typical (β/α) 8 barrel structure as active catalysts in starch breakdown, catalytically inactive BAMs are implicated in diverse yet elusive functions in plants. Further, the noncatalytic BAM7/8 contain N-terminal BZR1 domains and were shown to be involved in the regulation of brassinosteroid signaling and possibly serve as sensors of yet an uncharacterized metabolic signal. While the structures of several catalytically active BAMs have been reported, structural characterization of the catalytically inactive BZR1-type BAMs remain unknown. Here, we determine the crystal structure of β-amylase domain of Zea mays BAM8/BES1/BZR1-5 and provide comprehensive insights into its noncatalytic adaptation. Using structural-guided comparison combined with biochemical analysis and molecular dynamics simulations, we revealed conformational changes in multiple distinct highly conserved regions resulting in rearrangement of the binding pocket. Altogether, this study adds a new layer of understanding to starch breakdown mechanism and elucidates the acquired adjustments of noncatalytic BZR1-type BAMs as putative regulatory domains and/or metabolic sensors in plants.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS1997

Isolation of novel ribozymes that ligate AMP-activated RNA substrates

BACKGROUND: The protein enzymes RNA ligase and DNA ligase catalyze the ligation of nucleic acids via an adenosine-5'-5'-pyrophosphate 'capped' RNA or DNA intermediate. The activation of nucleic acid substrates by adenosine 5'-monophosphate (AMP) may be a vestige of 'RNA world' catalysis. AMP-activated ligation seems ideally suited for catalysis by ribozymes (RNA enzymes), because an RNA motif capable of tightly and specifically binding AMP has previously been isolated. RESULTS: We used in vitro selection and directed evolution to explore the ability of ribozymes to catalyze the template-directed ligation of AMP-activated RNAs. We subjected a pool of 10(15) RNA molecules, each consisting of long random sequences flanking a mutagenized adenosine triphosphate (ATP) aptamer, to ten rounds of in vitro selection, including three rounds involving mutagenic polymerase chain reaction. Selection was for the ligation of an oligonucleotide to the 5'-capped active pool RNA species. Many different ligase ribozymes were isolated; these ribozymes had rates of reaction up to 0.4 ligations per hour, corresponding to rate accelerations of approximately 5 x10(5) over the templated, but otherwise uncatalyzed, background reaction rate. Three characterized ribozymes catalyzed the formation of 3'-5'-phosphodiester bonds and were highly specific for activation by AMP at the ligation site. CONCLUSIONS: The existence of a new class of ligase ribozymes is consistent with the hypothesis that the unusual mechanism of the biological ligases resulted from a conservation of mechanism during an evolutionary replacement of a primordial ribozyme ligase by a more modern protein enzyme. The newly isolated ligase ribozymes may also provide a starting point for the isolation of ribozymes that catalyze the polymerization of AMP-activated oligonucleotides or mononucleotides, which might have been the prebiotic analogs of nucleoside triphosphates.

NASA Discipline Exobiology↗
DOE OSTI2025

Q -score as a reliability measure for protein, nucleic acid and small-molecule atomic coordinate models derived from 3DEM maps

Atomic coordinate models are important for the interpretation of 3D maps produced with cryoEM and cryoET (3D electron microscopy; 3DEM). In addition to visual inspection of such maps and models, quantitative metrics can inform about the reliability of the atomic coordinates, in particular how well the model is supported by the experimentally determined 3DEM map. A recently introduced metric, Q-score, was shown to correlate well with the reported resolution of the map for well fitted models. Here, we present new statistical analyses of Q-score based on its application to ∼10 000 maps and models archived in the EMDB (Electron Microscopy Data Bank) and PDB (Protein Data Bank). Further, we introduce two new metrics based on Q-score to represent each map and model relative to all entries in the EMDB and those with similar resolution. We explore through illustrative examples of proteins, nucleic acids and small molecules how Q-scores can indicate whether the atomic coordinates are well fitted to 3DEM maps and also whether some parts of a map may be poorly resolved due to factors such as molecular flexibility, radiation damage and/or conformational heterogeneity. These examples and statistical analyses provide a basis for how Q-scores can be interpreted effectively in order to evaluate 3DEM maps and atomic coordinate models prior to publication and archiving.

B factors↗
DOE OSTI2023

Molecular-dynamics simulation methods for macromolecular crystallography

It is investigated whether molecular-dynamics (MD) simulations can be used to enhance macromolecular crystallography (MX) studies. Historically, protein crystal structures have been described using a single set of atomic coordinates. Because conformational variation is important for protein function, researchers now often build models that contain multiple structures. Methods for building such models can fail, however, in regions where the crystallographic density is difficult to interpret, for example at the protein–solvent interface. To address this limitation, a set of MD–MX methods that combine MD simulations of protein crystals with conventional modeling and refinement tools have been developed. In an application to a cyclic adenosine monophosphate-dependent protein kinase at room temperature, the procedure improved the interpretation of ambiguous density, yielding an alternative water model and a revised protein model including multiple conformations. The revised model provides mechanistic insights into the catalytic and regulatory interactions of the enzyme. The same methods may be used in other MX studies to seek mechanistic insights.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Experimental and Computational Insights into the Structural Dynamics of the Fc Fragment of IgG1 Subtype from Biosimilar VEGF‐Trap

The constant fragment (Fc) of the immunoglobulin G1 (IgG1) subtype is increasingly recognized as a crucial scaffold in the development of advanced therapeutics due to its enhanced specificity, efficacy, and extended half‐life. A prime example is VEGF‐Trap (Aflibercept), a recombinant fusion protein that merges the Fc region of the IgG1 subtype with the binding domains of vascular endothelial growth factor receptors (VEGFR)‐1 and VEGFR‐2. The Fc region's role in N‐glycosylation is particularly important, as it significantly influences protein stability. Herein, the first near‐physiological temperature structures of the N‐glycan‐bound Fc fragment of IgG1 subtype from a biosimilar VEGF‐Trap are presented, determined using the SPring‐8 Angstrom Compact free electron LAser (SACLA) and the Turkish Light Source (Turkish DeLight). Comparative analysis with cryogenic structures, including existing data, reveals alternate conformations within the glycan‐binding pocket. Furthermore, molecular dynamics simulations indicate the presence of a high degree of structural plasticity, explaining how the protein adapts its structure through conformational changes. The observed structural fluctuations/conformational changes demonstrate the effect of N‐glycans on protein stability. These findings offer new insights into the molecular basis of Fc‐mediated functions and provide valuable information for the design of next‐generation therapeutics.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Hierarchical thermal-conductive polymer nanocomposites for thermal management

Managing heat in electrical conductors is a major challenge to meet the demands for sustainable energy use and electrical reliability, most notably power electronics and energy-critical electrical machines. Achieving such disparate functionalities, such as high temperature thermal and electrical reliability, require rational design and manufacturing of thermal conductor material and its hierarchical structures. Here we present hierarchical thermal-conductive nanocomposites, consisting of nanostructured ceramic conformal coating and aligned ultrahigh molecular weight polyethylene fiber, to tailor heat dissipation in electric conductors. The hybrid aligned thermal interface exhibits a highly desirable temperature dependent anisotropic high thermal conductivity with 0.98W m –1 K –1 and dielectric strength with 3.4. In addition, electrically insulating thermal interfaces demonstrate high-performing and reliable electrical systems under the dynamic load conditions. The surface temperature of heterogeneous ceramic-polymer encapsulated conductor is 17.8 °C lower than that of polymer-encapsulated conductor at the same electrical load. Consequently, the findings shown here hold great promises for directing heat extraction in electrical machine systems, advancing thermal management for emerging electronic applications.

36 MATERIALS SCIENCE↗
DOE OSTI2025

Chemically Enhanced Electrodialysis (CEED) for Recovery of Rare Earth Elements

Rare-earth elements are crucial for numerous technologically relevant industries including energy, electronics, and aerospace; however, both the supply and separation of rare earths are pressing challenges. The long-term goal of the collaborative project is to develop a novel approach to existing extraction behaviors. To achieve this goal, a class of electrodialysis membranes with novel ion-gating functionality will be developed and paired with a conventional electrodialysis strategy. The hypothesis of the work is that incorporating sequestrants of suitable structures at the surface of the electrodialysis membrane will enhance extraction efficiency for ions of interest. Our ability to prepare sequestrants of diverse conformations and to adapt their molecular structure for binding lanthanides renders the proposed technology a versatile method for selective ion separation. Our approach will enable an entirely new technological approach to the separation of valuable rare-earth elements.

36 MATERIALS SCIENCE↗
NASA NTRS2001

Substitution of Ribonucleotides in the T7 RNA Polymerase Promoter Element

A systematic analysis was carried out to examine the effects of ribonucleotide substitution at various locations within the promoter element for T7 RNA polymerase. Ribonucleotides could be introduced at most positions without significantly decreasing transcription efficiency. A critical window of residues that were intolerant of RNA substitution was defined for both the non-template and template strands of the promoter. These residues are involved in important contacts with the AT-rich recognition loop, specificity loop, and P-intercalating hairpin of the polymerase. These results highlight the malleability of T7 RNA polymerase in recognizing its promoter element and suggest that promoters with altered backbone conformations may be used in molecular biology applications that employ T7 RNA polymerase for in vitro transcription.

McGinness, Kathleen E.↗
NASA NTRS1983

An extensive galactic search for conformer II glycine

The most extensive galactic search reported to date for conformer II glycine, a higher energy form of the simplest amino acid has been conducted. The search utilized four glycine transitions at centimeter wavelengths and 21 at millimeter wavelengths to observe 18 galactic molecular sources and one comet. No conformer II glycine lines were detected, and measurements of representative sources were used to compute upper limits on total column densities. Several unidentified lines were detected and are reported here with some suggested possible identifications.

Snyder, L. E.↗
DOE OSTI2024

A modular and extensible CHARMM-compatible model for all-atom simulation of polypeptoids

Peptoids (N-substituted glycines) are a class of sequence-defined synthetic peptidomimetic polymers with applications including drug delivery, catalysis, and biomimicry. Classical molecular simulations have been used to predict and understand the conformational dynamics of single chains and their self-assembly into morphologies including sheets, tubes, spheres, and fibrils. The CGenFF-NTOID model based on the CHARMM General Force Field has demonstrated success in accurate all-atom molecular modeling of peptoid structure and thermodynamics. Extension of this force field to new peptoid side chains has historically required reparameterization of side chain bonded interactions against ab initio data. This fitting protocol improves the accuracy of the force field but is also burdensome and precludes modular extensibility of the model to arbitrary peptoid sequences. In this work, we develop and demonstrate a Modular Side Chain CGenFF-NTOID (MoSiC-CGenFF-NTOID) as an extension of CGenFF-NTOID employing a modular decomposition of the peptoid backbone and side chain parameterizations, wherein arbitrary side chains within the large family of substituted methyl groups (i.e., –CH 3 , –CH 2 R, –CHRR', and –CRR'R") are directly ported from CGenFF. We validate this approach against ab initio calculations and experimental data to develop a MoSiC-CGenFF-NTOID model for all 20 natural amino acid side chains along with 13 commonly used synthetic side chains and present an extensible paradigm to efficiently determine whether a novel side chain can be directly incorporated into the model or whether refitting of the CGenFF parameters is warranted. We make the model freely available to the community along with a tool to perform automated initial structure generation.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
NASA NTRS1997

Continuous in vitro evolution of catalytic function

A population of RNA molecules that catalyze the template-directed ligation of RNA substrates was made to evolve in a continuous manner in the test tube. A simple serial transfer procedure was used to achieve approximately 300 successive rounds of catalysis and selective amplification in 52 hours. During this time, the population size was maintained against an overall dilution of 3 x 10(298). Both the catalytic rate and amplification rate of the RNAs improved substantially as a consequence of mutations that accumulated during the evolution process. Continuous in vitro evolution makes it possible to maintain laboratory "cultures" of catalytic molecules that can be perpetuated indefinitely.

Non-NASA Center↗
DOE OSTI2025

Dynamics and activation of membrane-bound B cell receptor assembly

B-cell receptor (BCR) complexes are expressed on the surface of a B-cell and are critical in antigen recognition and modulating the adaptive immune response. Even though the relevance of antibodies has been known for almost a hundred years, the antigen-dependent activation mechanism of B-cells has remained elusive. Several models have been proposed for BCR activation, including cross-linking, conformation-induced oligomerization, and dissociation activation models. Recently, the first cryo-EM structures of the human B-cell antigen receptor of the IgM and IgG isotypes have been published that validates the asymmetric organization of the BCR complex. Here, we carry out extensive molecular dynamics simulations to probe the conformational changes upon antigen binding and the influence of the membrane lipids. We identify two critical dynamical events that could be associated with antigen-dependent activation of BCR. First, antigen binding causes increased flexibility in regions distal to the antigen binding site. Second, antigen binding alters the rearrangement of IgM transmembrane helices, including the relative interaction of Igα/Igβ that mediates intracellular signaling. Furthermore, these transmembrane rearrangements lead to changes in localized lipid composition. Our work indirectly supports the conformational-change induced models of BCR activation and contributes to the understanding of the antigen-dependent activation mechanism of BCRs.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS1993

Modeling study on the cleavage step of the self-splicing reaction in group I introns

A three-dimensional model of the Tetrahymena thermophila group I intron is used to further explore the catalytic mechanism of the transphosphorylation reaction of the cleavage step. Based on the coordinates of the catalytic core model proposed by Michel and Westhof (Michel, F., Westhof, E. J. Mol. Biol. 216, 585-610 (1990)), we first converted their ligation step model into a model of the cleavage step by the substitution of several bases and the removal of helix P9. Next, an attempt to place a trigonal bipyramidal transition state model in the active site revealed that this modified model for the cleavage step could not accommodate the transition state due to insufficient space. A lowering of P1 helix relative to surrounding helices provided the additional space required. Simultaneously, it provided a better starting geometry to model the molecular contacts proposed by Pyle et al. (Pyle, A. M., Murphy, F. L., Cech, T. R. Nature 358, 123-128. (1992)), based on mutational studies involving the J8/7 segment. Two hydrated Mg2+ complexes were placed in the active site of the ribozyme model, using the crystal structure of the functionally similar Klenow fragment (Beese, L.S., Steitz, T.A. EMBO J. 10, 25-33 (1991)) as a guide. The presence of two metal ions in the active site of the intron differs from previous models, which incorporate one metal ion in the catalytic site to fulfill the postulated roles of Mg2+ in catalysis. The reaction profile is simulated based on a trigonal bipyramidal transition state, and the role of the hydrated Mg2+ complexes in catalysis is further explored using molecular orbital calculations.

NASA Discipline Exobiology↗
NASA NTRS1988

Computer modeling of polymers

A Polymer Molecular Analysis Display System (p-MADS) was developed for computer modeling of polymers. This method of modeling allows for the theoretical calculation of molecular properties such as equilibrium geometries, conformational energies, heats of formations, crystal packing arrangements, and other properties. Furthermore, p-MADS has the following capabilities: constructing molecules from internal coordinates (bonds length, angles, and dihedral angles), Cartesian coordinates (such as X-ray structures), or from stick drawings; manipulating molecules using graphics and making hard copy representation of the molecules on a graphics printer; and performing geometry optimization calculations on molecules using the methods of molecular mechanics or molecular orbital theory.

Green, Terry J.↗
NASA NTRS1983

Molecular deformation and stress-strain behavior of poly(bisphenol-A-diphenyl sulfone)

The strain-birefringence response of poly(bisphenol-A-diphenyl sulfone) is found to be independent of temperature at temperatures below -100 C; at higher temperatures, the response becomes slightly dependent on temperature, with lower birefringence seen at higher temperatures. The stress-strain behavior and the stress-birefringence response both depend on temperature over the entire testing temperature range (-179 C to 150 C) studied; this dependence, however, is not pronounced. The evidence is seen as suggesting that the polymer molecules respond to deformation by undergoing conformational rearrangements; the mode of the molecular deformation remains unchanged for temperatures of -100 C or lower. At higher temperatures, the average length of the chain segments involved in the rearrangement increases. The stress-strain response is attributed mainly to chain orientation. The entropic contribution deriving from chain orientation at temperatures below -100 C is still substantial. The modest temperature dependence of the stress-strain response suggests that the energy barriers for the chain segments involved in the rearrangement are relatively low.

Hong, S.-D.↗