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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 793 records · Page 44
All sourcesNASA NTRSDOE OSTI
DOE OSTI2023

Data for Evaluation of 1,2-Diacyl-3-Acetyl Triacylglycerol Production in Yarrowia lipolytica

Plants produce many high-value oleochemical molecules. While oil-crop agriculture is performed at industrial scales, suitable land is not available to meet global oleochemical demand. Worse, establishing new oil-crop farms often comes with the environmental cost of tropical deforestation. The field of metabolic engineering offers tools to transplant oleochemical metabolism into tractable hosts while simultaneously providing access to molecules produced by non-agricultural plants. Here, we evaluate strategies for rewiring metabolism in the oleaginous yeast Yarrowia lipolytica to synthesize a foreign lipid, 3-acetyl-1,2-diacyl-sn-glycerol (acTAG). Oils made up of acTAG have a reduced viscosity and melting point relative to traditional triacylglycerol oils making them attractive as low-grade diesels, lubricants, and emulsifiers. This manuscript describes a metabolic engineering study that established acTAG production at g/L scale, exploration of the impact of lipid bodies on acTAG titer, and a techno-economic analysis that establishes the performance benchmarks required for microbial acTAG production to be economically feasible.

Biomass Analytics↗
DOE OSTI2024

Using data-science approaches to unravel insights for enhanced transport of lithium ions in single-ion conducting polymer electrolyte

Solid polymer electrolytes have yet to achieve the an ionic conductivity > 1 mS/cm at room temperature for realistic applications. This target implies the need to reduce the effective energy barriers of ion transport in polymer electrolytes to around 20 kJ/mol. In this work, we combine information extracted from existing experimental results with theoretical calculations to provide insights into ion transport in single-ion conductors (SICs) with a focus on lithium ion SICs. Through the analysis of temperature-dependent ionic conductivity data obtained from the literature, we evaluate different methods of extracting energy barriers for lithium transport. The traditional Arrhenius fit to the temperature-dependent ionic conductivity data indicates that the Meyer-Neldel rule holds for SICs. However, the values of the fitting parameters remain unphysical. Our modified approach based on recent work (Macromolecules, 56, 15, 6051(2023)), which incorporates a fixed pre-exponential factor, reveals that the energy barriers exhibit temperature dependence over a wide range of temperatures. Using this approach, we identify a series of anions leading to the energy barriers less than 30 kJ/mol, which include trifluoromethane sulfonimide (TFSI), fluoromethane sulfonimide (FSI), and boron-based organic anions. In our efforts to design the next generation of anions, which can exhibit the energy barriers less than 20 kJ/mol, we focused on boron-containing SICs, and performed density functional theory (DFT) based calculations to connect the chemical structures via the binding energy of cation (lithium)-anion pairs with the experimentally derived effective energy barriers for ion transport. Not only have we identified a correlation between the binding energy and the energy barriers, but we also propose a strategy to design new boron-based anions by using the correlation. This combined approach involving experiments and theoretical calculations is capable of facilitating the identification of promising new anions, which can exhibit ionic conductivity $> 1$ mS/cm near room temperature, thereby expediting the development of novel superionic single-ion conducting polymer electrolytes. The published datasets include all the temperature-dependent ionic conductivity collected from the literature with literature DOIs, DFT calculated binding energies, and python scripts to analyze data, construct statistical models, and generate plots.

36 MATERIALS SCIENCE↗
DOE OSTI2025

Full Rod Length Gamma Spectroscopy Measurements of LWR Used Fuel Rods

Twenty-five high-burnup pressurized water reactor used fuel rods were scanned in the Irradiated Fuels Examination Laboratory at Oak Ridge National Laboratory with a high-resolution gamma spectrometer. A planar high-purity germanium detector was used across an energy range from 60 keV to 3 MeV. Gamma spectra of individual fuel rods were collected in 4.5 mm steps along the entire length of each rod. Additional spectra were collected on select rods in rotational increments of 30 degrees to provide data on the distribution of fission products along the rod perimeter.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗
DOE OSTI2023

Enhancement of second-order optical nonlinearities and nanoscale periodic domain patterning in ferroelectric boron-substituted aluminum nitride thin films

The discovery and development of CMOS-compatible, nonlinear optical materials is essential to produce integrated photonic devices with advanced functionalities. AlN is a strong candidate for on-chip device demonstration due to its intrinsic second-order optical nonlinearities, large bandgap, and well-established fabrication techniques. However, AlN is not easily phase matched for the largest coefficient d 33 ; the coefficients that could potentially be dispersion phase-matched, d 31 and d 15 , have weak nonlinearities. This work investigates ferroelectric Al 1-x B x N (x = 0 to 0.11) for viability as a large bandgap nonlinear optical material with unique suitability towards ultraviolet light generation using second harmonic generation. The linear and nonlinear optical properties are characterized accounting for material anisotropy. With increasing B concentration, a large enhancement from near negligible values to d 31 = 0.9 ± 0.1 pm/V and d 15 = 1.2 ± 0.1 pm/V is observed. This compares favorably to other large bandgap materials like β-Ba(BO 2 ) 2 , where the largest nonlinear coefficient is d 22 ~ 2.3 pm/V at 800 nm. This is accompanied by a change in the bandgap from 6.1 eV to 5.8 eV as B substitution goes from 0 to 11%. A periodically poled, quasi-phase-matched ferroelectric domain pattern with 400 nm domain size and a wall roughness of <16 nm is demonstrated.

36 MATERIALS SCIENCE↗
DOE OSTI2025

Quantitative Nonlinear Optical Polarimetry with High Spatial Resolution

Nonlinear optical microscopy such as in the optical second-harmonic generation (SHG) modality has become a popular tool today for probing materials in the physical and biological sciences. While imaging and spectroscopy are widely used in the microscopy mode, nonlinear polarimetry, which can shed light on materials’ symmetry and microstructure, is relatively underdeveloped. This is partly because quantitative analytical modeling of the optical SHG response for anisotropic crystals and films largely assumes low-numerical aperture (NA) focusing of light, where the plane-wave approximation is sufficient. Tight focusing provides unique benefits in revealing out-of-plane polarization responses, which cannot be detected by near-plane-wave illumination at normal incidence. Here, we outline a method for quantitatively analyzing SHG polarimetry measurements obtained under high-NA focusing within a microscope geometry. Experiments and simulations of a variety of standard samples, from single crystals to thin films, are in good agreement, including measured and simulated spatial SHG maps of ferroelectric domains. A solution to the inverse problem is demonstrated, where the spatial distribution of an SHG tensor with unknown tensor coefficient magnitudes is determined by experimentally measured polarimetry. The ability to extract the out-of-plane component of the nonlinear polarization in normal incidence is demonstrated, which can be valuable for high-resolution polarimetry of 2D materials, thin films, heterostructures, and uniaxial crystals with a strong out-of-plane response.

36 MATERIALS SCIENCE↗
DOE OSTI2020

Structural analyses of the PKA RIIβ holoenzyme containing the oncogenic DnaJB1-PKAc fusion protein reveal protomer asymmetry and fusion-induced allosteric perturbations in fibrolamellar hepatocellular carcinoma

When the J-domain of the heat shock protein DnaJB1 is fused to the catalytic (C) subunit of cAMP-dependent protein kinase (PKA), replacing exon 1, this fusion protein, J-C subunit (J-C), becomes the driver of fibrolamellar hepatocellular carcinoma (FL-HCC). Here, we use cryo-electron microscopy (cryo-EM) to characterize J-C bound to RIIβ, the major PKA regulatory (R) subunit in liver, thus reporting the first cryo-EM structure of any PKA holoenzyme. We report several differences in both structure and dynamics that could not be captured by the conventional crystallography approaches used to obtain prior structures. Most striking is the asymmetry caused by the absence of the second cyclic nucleotide binding (CNB) domain and the J-domain in one of the RIIβ:J-C protomers. Using molecular dynamics (MD) simulations, we discovered that this asymmetry is already present in the wild-type (WT) RIIβ 2 C 2 but had been masked in the previous crystal structure. This asymmetry may link to the intrinsic allosteric regulation of all PKA holoenzymes and could also explain why most disease mutations in PKA regulatory subunits are dominant negative. The cryo-EM structure, combined with small-angle X-ray scattering (SAXS), also allowed us to predict the general position of the Dimerization/Docking (D/D) domain, which is essential for localization and interacting with membrane-anchored A-Kinase-Anchoring Proteins (AKAPs). This position provides a multivalent mechanism for interaction of the RIIβ holoenzyme with membranes and would be perturbed in the oncogenic fusion protein. The J-domain also alters several biochemical properties of the RIIβ holoenzyme: It is easier to activate with cAMP, and the cooperativity is reduced. These results provide new insights into how the finely tuned allosteric PKA signaling network is disrupted by the oncogenic J-C subunit, ultimately leading to the development of FL-HCC.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Crowdsourcing biocuration: The Community Assessment of Community Annotation with Ontologies (CACAO)

Experimental data about gene functions curated from the primary literature have enormous value for research scientists in understanding biology. Using the Gene Ontology (GO), manual curation by experts has provided an important resource for studying gene function, especially within model organisms. Unprecedented expansion of the scientific literature and validation of the predicted proteins have increased both data value and the challenges of keeping pace. Capturing literature-based functional annotations is limited by the ability of biocurators to handle the massive and rapidly growing scientific literature. Within the community-oriented wiki framework for GO annotation called the Gene Ontology Normal Usage Tracking System (GONUTS), we describe an approach to expand biocuration through crowdsourcing with undergraduates. This multiplies the number of high-quality annotations in international databases, enriches our coverage of the literature on normal gene function, and pushes the field in new directions. From an intercollegiate competition judged by experienced biocurators, Community Assessment of Community Annotation with Ontologies (CACAO), we have contributed nearly 5,000 literature-based annotations. Many of those annotations are to organisms not currently well-represented within GO. Over a 10-year history, our community contributors have spurred changes to the ontology not traditionally covered by professional biocurators. The CACAO principle of relying on community members to participate in and shape the future of biocuration in GO is a powerful and scalable model used to promote the scientific enterprise. It also provides undergraduate students with a unique and enriching introduction to critical reading of primary literature and acquisition of marketable skills.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Modeling suggests that virion production cycles within individual cells is key to understanding acute hepatitis B virus infection kinetics

Hepatitis B virus (HBV) infection kinetics in immunodeficient mice reconstituted with humanized livers from inoculation to steady state is highly dynamic despite the absence of an adaptive immune response. To recapitulate the multiphasic viral kinetic patterns, we developed an agent-based model that includes intracellular virion production cycles reflecting the cyclic nature of each individual virus lifecycle. The model fits the data well predicting an increase in production cycles initially starting with a long production cycle of 1 virion per 20 hours that gradually reaches 1 virion per hour after approximately 3–4 days before virion production increases dramatically to reach to a steady state rate of 4 virions per hour per cell. Together, modeling suggests that it is the cyclic nature of the virus lifecycle combined with an initial slow but increasing rate of HBV production from each cell that plays a role in generating the observed multiphasic HBV kinetic patterns in humanized mice.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Detecting multiple communities using quantum annealing on the D-Wave system

A very important problem in combinatorial optimization is the partitioning of a network into communities of densely connected nodes; where the connectivity between nodes inside a particular community is large compared to the connectivity between nodes belonging to different ones. This problem is known as community detection, and has become very important in various fields of science including chemistry, biology and social sciences. The problem of community detection is a twofold problem that consists of determining the number of communities and, at the same time, finding those communities. This drastically increases the solution space for heuristics to work on, compared to traditional graph partitioning problems. In many of the scientific domains in which graphs are used, there is the need to have the ability to partition a graph into communities with the “highest quality” possible since the presence of even small isolated communities can become crucial to explain a particular phenomenon. We have explored community detection using the power of quantum annealers, and in particular the D-Wave 2X and 2000Q machines. It turns out that the problem of detecting at most two communities naturally fits into the architecture of a quantum annealer with almost no need of reformulation. This paper addresses a systematic study of detecting two or more communities in a network using a quantum annealer.

97 MATHEMATICS AND COMPUTING↗
DOE OSTI2021

Interaction of amphiphilic lipoarabinomannan with host carrier lipoproteins in tuberculosis patients: Implications for blood-based diagnostics

Lipoarabinomannan (LAM), an amphiphilic lipoglycan of the Mycobacterium tuberculosis cell wall, is a diagnostic target for tuberculosis. Previous work from our laboratory and others suggests that LAM is associated with host serum lipoproteins, which may in turn have implications for diagnostic assays. Our team has developed two serum assays for amphiphile detection: lipoprotein capture and membrane insertion. The lipoprotein capture assay relies on capture of the host lipoproteins, exploiting the biological association of host lipoprotein with microbial amphiphilic biomarkers to “concentrate” LAM. In contrast, the membrane insertion assay is independent of the association between pathogen amphiphiles and host lipoprotein association, and directly captures LAM based on its thermodynamic propensity for association with a supported lipid membrane, which forms the functional surface of an optical biosensor. In this manuscript, we explored the use of these assays for the detection of LAM in sera from adults whose tuberculosis status had been well-characterized using conventional microbiological tests, and endemic controls. Using the lipoprotein capture assay, LAM signal/noise ratios were >1.0 in 29/35 (83%) individuals with culture-confirmed active tuberculosis, 8/13 (62%) individuals with tuberculosis symptoms, but no positive culture for M . tuberculosis , and 0/6 (0%) symptom-free endemic controls. To evaluate serum LAM levels without bias associated with potential differences in circulating host lipoprotein concentrations between individuals, we subsequently processed available samples to liberate LAM from associated host lipoprotein assemblies followed by direct detection of the pathogen biomarker using the membrane insertion approach. Using the membrane insertion assay, signal/noise for detection of serum LAM was greater than that observed using the lipoprotein capture method for culture-confirmed TB patients (6/6), yet remained negative for controls (2/2). Taken together, these results suggest that detection of serum LAM is a promising TB diagnostic approach, but that further work is required to optimize assay performance and to decipher the implications of LAM/host lipoprotein associations for diagnostic assay performance and TB pathogenesis.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Phylogenetic diversity, trichothecene potential, and pathogenicity within Fusarium sambucinum species complex

The Fusarium sambucinum species complex (FSAMSC) is one of the most taxonomically challenging groups of fusaria, comprising prominent mycotoxigenic plant pathogens and other species with various lifestyles. Among toxins produced by members of the FSAMSC, trichothecenes pose the most significant threat to public health. Herein a global collection of 171 strains, originating from diverse hosts or substrates, were selected to represent FSAMSC diversity. This strain collection was used to assess their species diversity, evaluate their potential to produce trichothecenes, and cause disease on wheat. Maximum likelihood and Bayesian analyses of a combined 3-gene dataset used to infer evolutionary relationships revealed that the 171 strains originally received as 48 species represent 74 genealogically exclusive phylogenetically distinct species distributed among six strongly supported clades: Brachygibbosum, Graminearum, Longipes, Novel, Sambucinum, and Sporotrichioides. Most of the strains produced trichothecenes in vitro but varied in type, indicating that the six clades correspond to type A, type B, or both types of trichothecene-producing lineages. Furthermore, five strains representing two putative novel species within the Sambucinum Clade produced two newly discovered type A trichothecenes, 15-keto NX-2 and 15-keto NX-3. Strains of the two putatively novel species together with members of the Graminearum Clade were aggressive toward wheat when tested for pathogenicity on heads of the susceptible cultivar Apogee. In planta, the Graminearum Clade strains produced nivalenol or deoxynivalenol and the aggressive Sambucinum Clade strains synthesized NX-3 and 15-keto NX-3. Other strains within the Brachygibbosum, Longipes, Novel, Sambucinum, and Sporotrichioides Clades were nonpathogenic or could infect the inoculated floret without spreading within the head. Moreover, most of these strains did not produce any toxin in the inoculated spikelets. These data highlight aggressiveness toward wheat appears to be influenced by the type of toxin produced and that it is not limited to members of the Graminearum Clade.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

COVID-19 Evidence Accelerator: A parallel analysis to describe the use of Hydroxychloroquine with or without Azithromycin among hospitalized COVID-19 patients

Background: The COVID-19 pandemic remains a significant global threat. However, despite urgent need, there remains uncertainty surrounding best practices for pharmaceutical interventions to treat COVID-19. In particular, conflicting evidence has emerged surrounding the use of hydroxychloroquine and azithromycin, alone or in combination, for COVID-19. The COVID-19 Evidence Accelerator convened by the Reagan-Udall Foundation for the FDA, in collaboration with Friends of Cancer Research, assembled experts from the health systems research, regulatory science, data science, and epidemiology to participate in a large parallel analysis of different data sets to further explore the effectiveness of these treatments. Methods: Electronic health record (EHR) and claims data were extracted from seven separate databases. Parallel analyses were undertaken on data extracted from each source. Each analysis examined time to mortality in hospitalized patients treated with hydroxychloroquine, azithromycin, and the two in combination as compared to patients not treated with either drug. Cox proportional hazards models were used, and propensity score methods were undertaken to adjust for confounding. Frequencies of adverse events in each treatment group were also examined. Results: Neither hydroxychloroquine nor azithromycin, alone or in combination, were significantly associated with time to mortality among hospitalized COVID-19 patients. No treatment groups appeared to have an elevated risk of adverse events. Conclusion: Administration of hydroxychloroquine, azithromycin, and their combination appeared to have no effect on time to mortality in hospitalized COVID-19 patients. Continued research is needed to clarify best practices surrounding treatment of COVID-19.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Sampling electronic structure quadratic unconstrained binary optimization problems (QUBOs) with Ocean and Mukai solvers

The most advanced D-Wave Advantage quantum annealer has 5000+ qubits, however, every qubit is connected to a small number of neighbors. As such, implementation of a fully-connected graph results in an order of magnitude reduction in qubit count. To compensate for the reduced number of qubits, one has to rely on special heuristic software such as qbsolv, the purpose of which is to decompose a large quadratic unconstrained binary optimization (QUBO) problem into smaller pieces that fit onto a quantum annealer. In this work, we compare the performance of the open-source qbsolv which is a part of the D-Wave Ocean tools and a new Mukai QUBO solver from Quantum Computing Inc. (QCI). The comparison is done for solving the electronic structure problem and is implemented in a classical mode (Tabu search techniques). The Quantum Annealer Eigensolver is used to map the electronic structure eigenvalue-eigenvector equation to a QUBO problem, solvable on a D-Wave annealer. We find that the Mukai QUBO solver outperforms the Ocean qbsolv with one to two orders of magnitude more accurate energies for all calculations done in the present work, both the ground and excited state calculations. This work stimulates the further development of software to assist in the utilization of modern quantum annealers.

97 MATHEMATICS AND COMPUTING↗
DOE OSTI2022

Controlled precision QUBO-based algorithm to compute eigenvectors of symmetric matrices

We describe an algorithm to compute the extremal eigenvalues and corresponding eigenvectors of a symmetric matrix which is based on solving a sequence of Quadratic Binary Optimization problems. This algorithm is robust across many different classes of symmetric matrices; It can compute the eigenvector/eigenvalue pair to essentially any arbitrary precision, and with minor modifications, can also solve the generalized eigenvalue problem. Performance is analyzed on small random matrices and selected larger matrices from practical applications.

97 MATHEMATICS AND COMPUTING↗
DOE OSTI2022

Two (or more) for one: Identifying classes of household energy- and water-saving measures to understand the potential for positive spillover

A key component of behavior-based energy conservation programs is the identification of target behaviors. A common approach is to target behaviors with the greatest energy-saving potential. The concept of behavioral spillover introduces further considerations, namely that adoption of one energy-saving behavior may increase (or decrease) the likelihood of other energy-saving behaviors. This research aimed to identify and describe household energy- and water-saving measure classes within which positive spillover is likely to occur (e.g., adoption of energy-efficient appliances may correlate with adoption of water-efficient appliances), and explore demographic and psychographic predictors of each. Nearly 1,000 households in a California city were surveyed and asked to report whether they had adopted 75 different energy- and/or water-saving measures. Principal Component Analysis and Network Analysis based on correlations between adoption of these diverse measures revealed and characterized eight water-energy-saving measure classes: Water Conservation, Energy Conservation, Maintenance and Management, Efficient Appliance, Advanced Efficiency, Efficient Irrigation, Green Gardening, and Green Landscaping. Understanding these measure classes can help guide behavior-based energy program developers in selecting target behaviors and designing interventions.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗
DOE OSTI2022

A QUBO formulation for top-τ eigencentrality nodes

The efficient calculation of the centrality or “hierarchy” of nodes in a network has gained great relevance in recent years due to the generation of large amounts of data. The eigenvector centrality (aka eigencentrality) is quickly becoming a good metric for centrality due to both its simplicity and fidelity. In this work we lay the foundations for solving the eigencentrality problem of ranking the importance of the nodes of a network with scores from the eigenvector of the network, using quantum computational paradigms such as quantum annealing and gate-based quantum computing. The problem is reformulated as a quadratic unconstrained binary optimization (QUBO) that can be solved on both quantum architectures. The results focus on correctly identifying a given number of the most important nodes in numerous networks given by the sparse vector solution of our QUBO formulation of the problem of identifying the top- τ highest eigencentrality nodes in a network on both the D-Wave and IBM quantum computers.

97 MATHEMATICS AND COMPUTING↗
DOE OSTI2024

Temporal serum neurofilament light chain concentrations in sheep inoculated with the agent of classical scrapie

Objective: Neurofilament light chain (Nf-L) has been used to detect neuroaxonal damage in the brain caused by physical injury or disease. The purpose of this study was to determine if serum Nf-L could be used as a biomarker for pre-symptomatic detection of scrapie in sheep. Methods: Four sheep with prion protein genotype AVQQ were intranasally inoculated with the classical scrapie strain x124. Blood was collected every 4 weeks until 44 weeks post-inoculation, at which point weekly collection commenced. Serum was analyzed using single molecule array (Quanterix SR-X) to evaluate Nf-L concentrations. Results: Scrapie was confirmed in each sheep by testing homogenized brainstem at the level of the obex with a commercially available enzyme immunoassay. Increased serum Nf-L concentrations were identified above the determined cutoff during the last tenth of the respective incubation period for each sheep. Throughout the time course study, PrP Sc accumulation was not detected antemortem by immunohistochemistry in rectal tissue at any timepoint for any sheep. RT-QuIC results were inconsistently positive throughout the timepoints tested for each sheep; however, each sheep had at least one timepoint detected positive. When assessing serum Nf-L utility using receiver operator characteristic curves against different clinical parameters, such as asymptomatic and symptomatic (pruritus or neurologic signs), results showed that Nf-L was most useful at being an indicator of disease only late in disease progression when neurologic signs were present. Conclusion: Serum Nf-L concentrations in the cohort of sheep increased as disease progressed; however, serum Nf-L did not increase during the presymptomatic window. The levels increased substantially throughout the final 10% of the animals’ scrapie incubation period when other clinical signs were present. Serum Nf-L is not a reliable biomarker for pre-clinical detection of scrapie.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Metadynamics simulations reveal mechanisms of Na + and Ca 2+ transport in two open states of the channelrhodopsin chimera, C1C2

Cation conducting channelrhodopsins (ChRs) are a popular tool used in optogenetics to control the activity of excitable cells and tissues using light. ChRs with altered ion selectivity are in high demand for use in different cell types and for other specialized applications. However, a detailed mechanism of ion permeation in ChRs is not fully resolved. Here, we use complementary experimental and computational methods to uncover the mechanisms of cation transport and valence selectivity through the channelrhodopsin chimera, C1C2, in the high- and low-conducting open states. Electrophysiology measurements identified a single-residue substitution within the central gate, N297D, that increased Ca 2+ permeability vs. Na + by nearly two-fold at peak current, but less so at stationary current. We then developed molecular models of dimeric wild-type C1C2 and N297D mutant channels in both open states and calculated the PMF profiles for Na + and Ca 2+ permeation through each protein using well-tempered/multiple-walker metadynamics. Results of these studies agree well with experimental measurements and demonstrate that the pore entrance on the extracellular side differs from original predictions and is actually located in a gap between helices I and II. Cation transport occurs via a relay mechanism where cations are passed between flexible carboxylate sidechains lining the full length of the pore by sidechain swinging, like a monkey swinging on vines. In the mutant channel, residue D297 enhances Ca 2+ permeability by mediating the handoff between the central and cytosolic binding sites via direct coordination and sidechain swinging. We also found that altered cation binding affinities at both the extracellular entrance and central binding sites underly the distinct transport properties of the low-conducting open state. This work significantly advances our understanding of ion selectivity and permeation in cation channelrhodopsins and provides the insights needed for successful development of new ion-selective optogenetic tools.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗