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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 127 records · Page 7
All sourcesNASA NTRSDOE OSTI
DOE OSTI2023

Effect of Solvent on the Interaction of Lignin with a Zeolite Nanosheet in the Condensed Phase

Lignin is the essential building block of lignocellulosic biomass, an excellent renewable source of different aromatic monomers for the polymer and biofuel industry. The depolymerization of lignin into value-added chemicals and fuels through the catalytic process poses a significant challenge due to the complex structure of lignin. Understanding lignin’s conformational diversity and dynamics in the liquid phase is crucial to designing an effective depolymerization process. Here, we conducted all-atom molecular dynamics simulations to understand the conformation and dynamics of softwood lignin on the all-silica zeolite nanosheet based on the MFI topology in a binary mixture of water–methanol at three different molar compositions (0%, 50%, and 100% methanol). We observed that the methanol–surface interaction is stronger than the water–surface interaction, and methanol readily diffused into the MFI core. Lignin surface contacts decrease with increasing methanol composition due to higher solubility and dynamics. Lignin dynamics on the surface in neat water is an order of magnitude smaller than methanol. Here, we also found that lignin adopts a slightly extended conformation when it stays on the surface than in the bulk solution phase for the pure water case, whereas for pure methanol and the binary solution structures are statistically similar.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2023

Atomistic Simulations of Polydisperse Lignin Melts Using Simple Polydisperse Residue Input Generator

Understanding the physics of lignin will help rationalize its function in plant cell walls as well as aiding practical applications such as deriving biofuels and bioproducts. Here, in this work, we present SPRIG (Simple Polydisperse Residue Input Generator), a program for generating atomic-detail models of random polydisperse lignin copolymer melts i.e., the state most commonly found in nature. Using these models, we use all-atom molecular dynamics (MD) simulations to investigate the conformational and dynamic properties of polydisperse melts representative of switchgrass (Panicum virgatum L.) lignin. Polydispersity, branching and monolignol sequence are found to not affect the calculated glass transition temperature, T g . The Flory–Huggins scaling parameter for the segmental radius of gyration is 0.42 ± 0.02, indicating that the chains exhibit statistics that lie between a globular chain and an ideal Gaussian chain. Below T g the atomic mean squared displacements are independent of molecular weight. In contrast, above T g , they decrease with increasing molecular weight. Therefore, a monodisperse lignin melt is a good approximation to this polydisperse lignin when only static properties are probed, whereas the molecular weight distribution needs to be considered while analyzing lignin dynamics.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2022

Identification of structural transitions in bacterial fatty acid binding proteins that permit ligand entry and exit at membranes

Fatty acid (FA) transfer proteins extract FA from membranes and sequester them to facilitate their movement through the cytosol. Detailed structural information is available for these soluble protein–FA complexes, but the structure of the protein conformation responsible for FA exchange at the membrane is unknown. Staphylococcus aureus FakB1 is a prototypical bacterial FA transfer protein that binds palmitate within a narrow, buried tunnel. Here, we define the conformational change from a “closed” FakB1 state to an “open” state that associates with the membrane and provides a path for entry and egress of the FA. Using NMR spectroscopy, we identified a conformationally flexible dynamic region in FakB1, and X-ray crystallography of FakB1 mutants captured the conformation of the open state. In addition, molecular dynamics simulations show that the new amphipathic α-helix formed in the open state inserts below the phosphate plane of the bilayer to create a diffusion channel for the hydrophobic FA tail to access the hydrocarbon core and place the carboxyl group at the phosphate layer. The membrane binding and catalytic properties of site-directed mutants were consistent with the proposed membrane docked structure predicted by our molecular dynamics simulations. Finally, the structure of the bilayer-associated conformation of FakB1 has local similarities with mammalian FA binding proteins and provides a conceptual framework for how these proteins interact with the membrane to create a diffusion channel from the FA location in the bilayer to the protein interior.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2021

Chain and Segmental Dynamics in Polymer–Nanoparticle Composites with High Nanoparticle Loading

Recent experimental and simulation studies have shown that polymer–nanoparticle (NP) composites (PNCs) with ultra-high NP loading (>50%) exhibit remarkable mechanical properties and dramatic increases in polymer glass-transition temperature, viscosity, and thermal stability compared to the bulk polymer. These deviations in macroscopic properties suggest a slowdown in both segmental and chain-scale polymer dynamics due to confinement. In this work, we examine the polymer conformations and dynamics in these PNCs using molecular dynamics simulations of both unentangled and entangled coarse-grained polymers in random-close-packed NP packings with varying polymer fill fractions. We find that the changes in the polymer dynamics depend on the number of NPs in contact with a polymer segment. Using the number of polymer–NP contacts and different polymer chain conformations as criteria for categorization, we further examine the polymer dynamics at multiple length scales to show the high level of dynamic heterogeneity in PNCs with ultra-high NP loading.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2020

Molecular recognition of a host protein by NS1 of pandemic and seasonal influenza A viruses

The 1918 influenza A virus (IAV) caused the most severe flu pandemic in recorded human history. Nonstructural protein 1 (NS1) is an important virulence factor of the 1918 IAV. NS1 antagonizes host defense mechanisms through interactions with multiple host factors. One pathway by which NS1 increases virulence is through the activation of phosphoinositide 3-kinase (PI3K) by binding to its p85β subunit. Here we present the mechanism underlying the molecular recognition of the p85β subunit by 1918 NS1. Using X-ray crystallography, we determine the structure of 1918 NS1 complexed with p85β of human PI3K. We find that the 1918 NS1 effector domain (1918 NS1 ED ) undergoes a conformational change to bind p85β. Using NMR relaxation dispersion and molecular dynamics simulation, we identify that free 1918 NS1 ED exists in a dynamic equilibrium between p85β-binding–competent and –incompetent conformations in the submillisecond timescale. Moreover, we discover that NS1 ED proteins of 1918 (H1N1) and Udorn (H3N2) strains exhibit drastically different conformational dynamics and binding kinetics to p85β. These results provide evidence of strain-dependent conformational dynamics of NS1. Using kinetic modeling based on the experimental data, we demonstrate that 1918 NS1 ED can result in the faster hijacking of p85β compared to Ud NS1 ED , although the former has a lower affinity to p85β than the latter. Our results suggest that the difference in binding kinetics may impact the competition with cellular antiviral responses for the activation of PI3K. We anticipate that our findings will increase the understanding of the strain-dependent behaviors of influenza NS1 proteins.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Integrating Ultra-Coarse-Grained Protein Models into Accessible Workflows for Multiscale Molecular Dynamics

To capture protein conformational transitions using molecular dynamics (MD), several simulation resolutions covering different spatial and temporal scales are typically needed. All-atom (AA) simulations provide fine resolution, but are computationally infeasible for large systems over longer durations. Coarse-grained (CG) and ultra-coarse-grained (UCG) models have a lower resolution and computational cost while still being able to conserve essential protein features. Prior work on a Multiscale Machinelearned Modeling Infrastructure (MuMMI) combined both AA and CG simulations to study RAS-RAF protein interactions, leveraging CG models for longer time scales and using AA to investigate unusual conformations in greater detail. However, MuMMI is still resource-intensive, and this study aims to maximize exploration of the protein conformational space while reducing computational cost. In this paper, we build on prior work that integrates UCG models based on heterogeneous elastic network modeling (hENM) into the MuMMI workflow. We demonstrate that UCG models enable accurate sampling of protein conformations, focusing on simulating RAS-RAF protein interactions. Using higher-resolution CG Martini simulation data, we can automatically refine intramolecular interactions in UCG models. We present a scalable Python package that uses fluctuations observed in higher-resolution CG Martini simulations to estimate bond coefficients of the UCG model. We built novel machine learning-based backmapping methods to recover more detailed CG Martini structures from UCG structures, using diffusion models to learn the mapping between scales. Finally, we present UCG-mini-MuMMI, an accessible and less compute-intensive version of MuMMI as a resource for the scientific community. Incorporating UCG models into MD studies is applicable to a broad range of systems and proteins, and our study offers insights into the advantages and limitations of these methods.

Chemical structure↗
DOE OSTI2024

Shape-persistent ladder molecules exhibit nanogap-independent conductance in single-molecule junctions

Molecular electronic devices require precise control over the flow of current in single molecules. However, the electron transport properties of single molecules critically depend on dynamic molecular conformations in nanoscale junctions. Here, in this work, we report a unique strategy for controlling molecular conductance using shape-persistent molecules. Chemically diverse, charged ladder molecules, synthesized via a one-pot multicomponent ladderization strategy, show a molecular conductance (d[log( G/G 0 )]/d x ≈ -0.1 nm -1 ) that is nearly independent of junction displacement, in stark contrast to the nanogap-dependent conductance (d[log( G/G 0 )]/d x ≈ -7 nm -1 ) observed for non-ladder analogues. Ladder molecules show an unusually narrow distribution of molecular conductance during dynamic junction displacement, which is attributed to the shape-persistent backbone and restricted rotation of terminal anchor groups. These principles are further extended to a butterfly-like molecule, thereby demonstrating the strategy's generality for achieving gap-independent conductance. Overall, our work provides important avenues for controlling molecular conductance using shape-persistent molecules. Achieving robust and controllable conductance in single-molecule junctions is challenging due to the dynamic nature of molecular conformations that fluctuate over operational timescales. A strategy using shape-persistent molecules has now been developed that demonstrates nearly junction-displacement-independent conductance, providing a stable solution for single-molecule electronic properties.

molecular electronics↗
DOE OSTI2021

Conformer-specific photochemistry imaged in real space and time

Conformation-dependent dynamics play an important role in organic chemistry syntheses such as electrocyclic reactions, as well as in biological processes such as protein folding. However, current time-resolved experimental methods struggle to distinguish conformers from each other, and conformational isomerism is usually analyzed through reactant and product distributions. Using a combination of mega–electron volt ultrafast electron diffraction and quantum wave packet simulations, Champenois et al. directly followed the photochemical electrocyclic ring opening of the molecule α-phellandrene with femtosecond time resolution and confirmed that the transformation of a specific molecular conformer follows the famous Woodward-Hoffmann rules. The proposed method is potentially a powerful tool to follow conformer specificity in various organic and biological systems in real time.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2026

Local Chain Dynamics in Sequence-Controlled Polymers as a Tunable Handle for Rare Earth Sequestration

Chain dynamics govern the intricate behaviors of proteins, underpinning functions such as catalysis, recognition, and stimulus response, and are an increasingly appreciated aspect of structure–function relationships. Analogously, manipulating chain dynamics and structure in abiotic polymers via sequence control is an exciting, yet underexplored, strategy for improving material functions. In this work, we report a systematic study relating the sequence of polymeric sequestrants to their structure and dynamics, as well as to their binding affinity and selectivity for model substrates, rare earth elements (REEs). A series of sequence-controlled polymers with metal chelating, solubilizing, and structure forming monomers was synthesized via multiblock polymerization, yielding compositionally identical polymers with spectroscopically resolved domains and distinct morphologies. Using a combination of small-angle X-ray scattering and 19 F NMR relaxometry measurements, we connected differences in polymer structure and dynamics to polymer sequence variables such as the patchiness (density) of the structure forming monomer and the location of the chelating monomer. Furthermore, we found that, relative to calcium, all polymers in the series collapse more and have slower dynamics when binding REEs (lanthanum and lutetium) , though the extent of these effects were sequence-dependent and localized to specific domains within the polymer. Notably, sequence-controlled polymers that exhibited the largest conformational and dynamic changes upon binding REEs also bound REEs with the greatest affinity and modest selectivity. Collectively, these results correlate monomer patterning with dynamics, morphology, and REE binding performance en route to the development of efficient and selective macromolecular chelators.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2023

Comparative Study of High-Resolution LysB29(Nε-myristoyl) des(B30) Insulin Structures Display Novel Dynamic Causal Interrelations in Monomeric-Dimeric Motions

The treatment of insulin-dependent diabetes mellitus is characterized by artificial supplementation of pancreatic β-cell ability to regulate sugar levels in the blood. Even though various insulin analogs are crucial for reasonable glycemic control, understanding the dynamic mechanism of the insulin analogs may help to improve the best-protracted insulin analog to assist people with type 1 diabetes (T1D) to live comfortably while maintaining tight glycemic control. Here, we present the high-resolution crystal structure of NN304, known as insulin detemir, to 1.7 Å resolution at cryogenic temperature. We computationally further investigated our crystal structure’s monomeric-dimeric conformation and dynamic profile by comparing it with a previously available detemir structure (PDB ID: 1XDA). Our structure (PDB ID: 8HGZ), obtained at elevated pH, provides electrostatically triggered minor movements in the equilibrium between alternate conformational substates compared to the previous structure, suggesting it might induce an intermediate state in the dissociation pathway of the insulin detemir’s hexamer:dihexamer equilibrium. Supplemented with orientational cross-correlation analysis by a Gaussian network model (GNM), this alternate oligomeric conformation offers the distinct cooperative motions originated by loose coupling of distant conformational substates of a protracted insulin analog that has not been previously observed.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

All-Atom Simulations Uncover Structural and Dynamical Properties of STING Proteins in the Membrane System

Recent studies have shown that the stimulator of interferon gene (STING) protein plays a central role in the immune system by facilitating the production of type I interferons in cells. The STING signaling pathway is also a prominent activator of cancer-killing T cells that initiate a powerful adaptive immune response. Since biomolecular signaling pathways are complicated and not easily identified through traditional experiments, molecular dynamics (MD) has often been used to study structural and dynamical responses of biological pathways. In this work, we carried out MD simulations for full-length chicken and human STING (chSTING and hSTING) proteins. Specifically, we investigated ligand-bound closed (holo) and ligand-unbound open (apo) forms of STING in the membrane system by comparing their conformational and dynamical differences. Our research provides clues for understanding the mechanism of the STING signaling pathway by uncovering detailed insights for the examined systems: the residues from each chain in the binding pocket are strongly correlated to one another in the open STING structure compared with those in the closed STING structure. Ligand-bound closed STING displays ~174° rotation of the ligand-binding domain (LBD) relative to the open STING structure. The dynamical analysis of residue Cys148 located in the linker region of hSTING does not support the earlier hypothesis that Cys148 can form disulfide bonds between adjacent STING dimers. We also demonstrate that using the full-length proteins is critical, since the MD simulations of the LBD portion alone cannot properly describe the global conformational properties of STING.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2021

Unveiling the Dynamics of KRAS4b on Lipid Model Membranes

Abstract Small GTPase proteins are ubiquitous and responsible for regulating several processes related to cell growth and differentiation. Mutations that stabilize their active state can lead to uncontrolled cell proliferation and cancer. Although these proteins are well characterized at the cellular scale, the molecular mechanisms governing their functions are still poorly understood. In addition, there is limited information about the regulatory function of the cell membrane which supports their activity. Thus, we have studied the dynamics and conformations of the farnesylated KRAS4b in various membrane model systems, ranging from binary fluid mixtures to heterogeneous raft mimics. Our approach combines long time-scale coarse-grained (CG) simulations and Markov state models to dissect the membrane-supported dynamics of KRAS4b. Our simulations reveal that protein dynamics is mainly modulated by the presence of anionic lipids and to some extent by the nucleotide state (activation) of the protein. In addition, our results suggest that both the farnesyl and the polybasic hypervariable region (HVR) are responsible for its preferential partitioning within the liquid-disordered (Ld) domains in membranes, potentially enhancing the formation of membrane-driven signaling platforms. Graphic Abstract

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Vascular K ATP channel structural dynamics reveal regulatory mechanism by Mg-nucleotides

Vascular tone is dependent on smooth muscle K ATP channels comprising pore-forming Kir6.1 and regulatory SUR2B subunits, in which mutations cause Cantú syndrome. Unique among K ATP isoforms, they lack spontaneous activity and require Mg-nucleotides for activation. Structural mechanisms underlying these properties are unknown. Here, we determined cryogenic electron microscopy structures of vascular K ATP channels bound to inhibitory ATP and glibenclamide, which differ informatively from similarly determined pancreatic K ATP channel isoform (Kir6.2/SUR1). Unlike SUR1, SUR2B subunits adopt distinct rotational “propeller” and “quatrefoil” geometries surrounding their Kir6.1 core. The glutamate/aspartate-rich linker connecting the two halves of the SUR-ABC core is observed in a quatrefoil-like conformation. Molecular dynamics simulations reveal MgADP-dependent dynamic tripartite interactions between this linker, SUR2B, and Kir6.1. The structures captured implicate a progression of intermediate states between MgADP-free inactivated, and MgADP-bound activated conformations wherein the glutamate/aspartate-rich linker participates as mobile autoinhibitory domain, suggesting a conformational pathway toward K ATP channel activation.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Nonlinear Shear Rheology of Entangled Polymer Rings

Steady-state shear viscosity η($\bar{γ}$) of unconcatenated ring polymer melts as a function of the shear rate $\bar{γ}$ is studied by a combination of experiments, simulations, and theory. Experiments using polystyrenes with Z ≈ 5 and Z ≈ 11 entanglements indicate weaker shear thinning for rings compared to linear polymers exhibiting power law scaling of shear viscosity η ~ $\bar{γ}$ –0.56 ± 0.02 , independent of chain length, for Weissenberg numbers up to about 10 2 . Nonequilibrium molecular dynamics simulations using the bead-spring model reveal a similar behavior with η ~ $\bar{γ}$ -0.57 ± 0.08 for 4 ≤ Z ≤ 57. Viscosity decreases with chain length for high $\bar{γ}$. In our experiments, we see the onset of this regime, and in simulations, which we extended to Wi ~ 10 4 , the nonuniversality is fully developed. In addition to a naive scaling theory yielding for the universal regime η ~ $\bar{γ}$ –0.57 , we developed a novel shear slit model explaining many details of observed conformations and dynamics as well as the chain length-dependent behavior of viscosity at large $\bar{γ}$. The signature feature of the model is the presence of two distinct length scales: the size of tension blobs and much larger thickness of a shear slit in which rings are self-consistently confined in the velocity gradient direction and which is dictated by the size of a chain section with relaxation time 1/$\bar{γ}$. These two length scales control the two normal stress differences. In this model, the chain length-dependent onset of nonuniversal behavior is set by tension blobs becoming as small as about one Kuhn segment. This model explains the approximate applicability of the Cox–Merz rule for ring polymers.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2021

Determination of the chemical shift tensor anisotropy and asymmetry of strongly dipolar coupled protons under fast MAS

Orientationally-dependent interactions such as dipolar coupling, quadrupolar coupling, and chemical shift anisotropy (CSA) contain a wealth of spatial information that can be used to elucidate molecular conformations and dynamics. To determine the sign of the chemical shift tensor anisotropy parameter (δ aniso ), both the |m| = 1 and |m| = 2 components of the CSA need to be symmetry allowed, while the recoupling of the |m| = 1 term is accompanied with the reintroduction of homonuclear dipolar coupling components. Therefore, previously suggested sequences which solely recouple the |m| = 2 term cannot determine the sign a 1 H's δ aniso in a densely-coupled network. Here, we demonstrate the CSA recoupling of strongly dipolar coupled 1 H spins using the $Cn^1_n (90_{0}360_{180}540_{0}360_{180}90_{0})$ sequence. This pulse scheme recouples both the |m| = 1 and |m| = 2 CSA terms but the scaling factors for the homonuclear dipolar coupling terms are zeroed. Consequently, the sequence is sensitive to the sign of δ aniso but is not influenced by homonuclear dipolar interactions.

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