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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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47 records · Page 3
All sourcesNASA NTRSDOE OSTI
DOE OSTI2020

Enhancing Terminal Deoxynucleotidyl Transferase Activity on Substrates with 3′ Terminal Structures for Enzymatic De Novo DNA Synthesis

Enzymatic oligonucleotide synthesis methods based on the template-independent polymerase terminal deoxynucleotidyl transferase (TdT) promise to enable the de novo synthesis of long oligonucleotides under mild, aqueous conditions. Intermediates with a 3′ terminal structure (hairpins) will inevitably arise during synthesis, but TdT has poor activity on these structured substrates, limiting its usefulness for oligonucleotide synthesis. Here, we described two parallel efforts to improve the activity of TdT on hairpins: (1) optimization of the concentrations of the divalent cation cofactors and (2) engineering TdT for enhanced thermostability, enabling reactions at elevated temperatures. By combining both of these improvements, we obtained a ~10-fold increase in the elongation rate of a guanine-cytosine hairpin.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Elioraea tepida , sp. nov., a Moderately Thermophilic Aerobic Anoxygenic Phototrophic Bacterium Isolated from the Mat Community of an Alkaline Siliceous Hot Spring in Yellowstone National Park, WY, USA

Strain MS-P2 T was isolated from microbial mats associated with Mushroom Spring, an alkaline siliceous hot spring in Yellowstone National Park, WY, USA. The isolate grows chemoheterotrophically by oxygen-dependent respiration, and light stimulates photoheterotrophic growth under strictly oxic conditions. Strain MS-P2 T synthesizes bacteriochlorophyll a and the carotenoid spirilloxanthin. However, photoautotrophic growth did not occur under oxic or anoxic conditions, suggesting that this strain should be classified as an aerobic anoxygenic phototrophic bacterium. Strain MS-P2 T cells are motile, curved rods about 0.5 to 1.0 μm wide and 1.0 to 1.5 μm long. The optimum growth temperature is 45–50 °C, and the optimum pH for growth is circum-neutral (pH 7.0–7.5). Sequence analysis of the 16S rRNA gene revealed that strain MS-P2 T is closely related to Elioraea species, members of the class Alphaproteobacteria, with a sequence identity of 96.58 to 98%. The genome of strain MS-P2 T is a single circular DNA molecule of 3,367,643 bp with a mol% guanine-plus-cytosine content of 70.6%. Based on phylogenetic, physiological, biochemical, and genomic characteristics, we propose this bacteriochlorophyll a-containing isolate is a new species belonging to the genus Elioraea, with the suggested name Elioraeatepida. The type-strain is strain MS-P2 T (= JCM33060 T = ATCC TSD-174 T ).

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Bubble Relaxation Dynamics in Homopolymer DNA Sequences

Understanding the inherent timescales of large bubbles in DNA is critical to a thorough comprehension of its physicochemical characteristics, as well as their potential role on helix opening and biological function. In this work, we employ the coarse-grained Peyrard–Bishop–Dauxois model of DNA to study relaxation dynamics of large bubbles in homopolymer DNA, using simulations up to the microsecond time scale. By studying energy autocorrelation functions of relatively large bubbles inserted into thermalised DNA molecules, we extract characteristic relaxation times from the equilibration process for both adenine–thymine (AT) and guanine–cytosine (GC) homopolymers. Bubbles of different amplitudes and widths are investigated through extensive statistics and appropriate fittings of their relaxation. Characteristic relaxation times increase with bubble amplitude and width. We show that, within the model, relaxation times are two orders of magnitude longer in GC sequences than in AT sequences. Overall, our results confirm that large bubbles leave a lasting impact on the molecule’s dynamics, for times between 0.5–500 ns depending on the homopolymer type and bubble shape, thus clearly affecting long-time evolutions of the molecule.

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

The relationship between gene traits and transcription in soil microbial communities varies by environmental stimulus

Codon and nucleotide frequencies are known to relate to the rate of gene transcription, yet how these traits shape transcriptional profiles of soil microbial communities remains unclear. Here we test the prediction that functional genes with high codon optimization and energetically lower cost nucleotides (i.e., nucleotides requiring less adenosine triphosphate (ATP) for synthesis) have higher transcriptional expression in a soil microbial community. In laboratory incubations, we subjected an agricultural soil to two separate short-term environmental changes: labile carbon (glucose) addition or a sudden 30-min increase in temperature from 20 °C to 60 °C. Using the total genomic codon frequencies to predict preferred codon usage for each taxon, we then estimated codon optimization for each transcript. On the community level, we found a higher average level of codon optimization after the addition of glucose. Synonymous nucleotide composition in the transcript pool also shifted towards energetically cheaper nucleotides, favoring uracil (U) over adenine (A) and cytosine (C) over guanine (G). Similarly, we found that encoded amino acid usage shifted towards energetically cheaper amino acids in response to labile carbon. In contrast, in communities responding to heat shock, there were no significant differences in the averaged gene traits of expressed transcripts. We used metagenome-assembled-genomes to further examine the ability of gene traits to predict transcriptional responses within and between taxa. We found that traits of individual genes could not reliably predict the level of transcription of a gene within or between taxa—highlighting the limits of this approach. However, we did find that when traits were averaged across several related genes, codon optimization was able to predict levels of transcription in metabolic pathways associated with growth and nutrient uptake in response to glucose. Similar relationships were not observed in response to heat, or for functions associated with stress—such as genes associated with sporulation or heat shock. These results demonstrate that gene traits, such as codon usage, nucleotide selection, and amino acid selection, relate to the transcriptional expression of genes in soil microbial communities and suggests that these relationships may be dependent on both gene function and the specific type of environmental stimuli.

Biological and medical sciences↗
DOE OSTI2024

Analytic Gradients for Equation-of-Motion Coupled Cluster with Single, Double, and Perturbative Triple Excitations

Understanding the process of molecular photoexcitation is crucial in various fields, including drug development, materials science, photovoltaics, and more. The electronic vertical excitation energy is a critical property, for example in determining the singlet-triplet gap of chromophores. However, a full understanding of excited-state processes requires additional explorations of the excited-state potential energy surface and electronic properties, which is greatly aided by the availability of analytic energy gradients. Owing to its robust high accuracy over a wide range of chemical problems, equation-of-motion coupled-cluster with single and double excitations (EOM-CCSD) is a powerful method for predicting excited state properties, and the implementation of analytic gradients of many EOM-CCSD (excitation energies, ionization potentials, electron attachment energies, etc.) along with numerous successful applications high- lights the flexibility of the method. In specific cases where a higher level of accuracy is needed or in more complex electronic structures, the inclusion of triple excitations becomes essential, for example, in the EOM-CCSD* approach of Saeh and Stanton. In this work, we derive and implement for the first time the analytic gradients of EOMEE-CCSD*, which also provides a template for analytic gradients of related ex- cited state methods with perturbative triple excitations. Here, the capabilities of analytic EOMEE-CCSD* gradients are illustrated by several representative examples.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2025

Spatial Signatures of Electron Correlation in Least-Squares Tensor Hypercontraction

Least Squares Tensor Hypercontraction (LS-THC) has received some attention in recent years as an approach to reduce the significant computational costs of wavefunc- tion based methods in quantum chemistry. However, previous work has demonstrated that the LS-THC factorization performs disproportionately worse in the description of wavefunction components (e.g. cluster amplitudes T 2 ) than Hamiltonian compo- nents (e.g. electron repulsion integrals (pq|rs)). This work develops novel theoretical methods to study the source of these errors in the context of the real-space T 2 kernel, and reports, for the first time, the existence of a “correlation feature” in the errors of the LS-THC representation of the “exchange-like” correlation energy EX and T 2 that is remarkably consistent across ten molecular species, three correlated wavefunctions, and four basis sets. This correlation feature portends the existence of a “pair-point kernel” missing in the usual LS-THC representation of the wavefunction, which critically depends upon pairs of grid points situated close to atoms and with inter-pair distances between one and two Bohr radii. These findings point the way for future LS-THC developments to address these shortcomings.

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

Interrupted DNA and Slow Silver Cluster Luminescence

A DNA–silver cluster conjugate is a hierarchical chromophore with a partly reduced silver core embedded within the DNA nucleobases that are covalently linked by the phosphodiester backbone. Specific sites within a polymeric DNA can be targeted to spectrally tune the silver cluster. Here, the repeated (C 2 A) 6 strand is interrupted with a thymine, and the resulting (C 2 A) 2 -T-(C 2 A) 4 forms only Ag 10 6+ , a chromophore with both prompt (~1 ns) green and sustained (~10 2 μs) red luminescence. Thymine is an inert placeholder that can be removed, and the two fragments (C 2 A) 2 and (C 2 A) 4 also produce the same Ag 10 6+ adduct. In relation to (C 2 A) 2 T(C 2 A) 4 , the (C 2 A) 2 + (C 2 A) 4 pair is distinguished because the red Ag 10 6+ luminescence is ~6× lower, relaxes ~30% faster, and is quenched ~2× faster with O 2 . These differences suggest that a specific break in the phosphodiester backbone can regulate how a contiguous vs broken scaffold wraps and better protects its cluster adduct.

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

Sodium Cationization Enables Exotic Deprotonation Sites on Gaseous Mononucleotides

In this work, we report observation and photoelectron spectroscopic characterization of sodium cationization on four doubly deprotonated mononucleotide dianions Na + ·[dNMP-2H] 2- (N = A, G, C, or T) in the gas phase. Multiple tautomers with distinct deprotonated sites are identified, in which Na+ enables novel double deprotonation patterns and folds resultant mononucleotide dianions. The most stable isomer for the whole family is derived from detaching one proton from phosphate and the other from nucleobase (amino group for N = A, G and C, but nitrogen atom for T), while a high-lying isomer with protons detached separately from phosphate and hydroxy group of sugar coexist. Particularly, an exotic deprotomer with both protons deprived from guanosine is populated as well. This work thus displays a remarkably diverse binding landscape enabled by sodium cationization, a potentially critical element in developing general formulism to better model metal cation and nucleotide interactions.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2024

Diaminopurine in Nonenzymatic RNA Template Copying

In the RNA World before the emergence of an RNA polymerase, nonenzymatic template copying would have been essential for the transmission of genetic information. However, the products of chemical copying with the canonical nucleotides (A, U, C, and G) are heavily biased toward the incorporation of G and C, which form a more stable base pair than A and U. We therefore asked whether replacing adenine (A) with diaminopurine (D) might lead to more efficient and less biased nonenzymatic template copying by making a stronger version of the A:U pair. As expected, primer extension substrates containing D bound to U in the template more tightly than substrates containing A. However, primer extension with D exhibited elevated reaction rates on a C template, leading to concerns about fidelity. Our crystallographic studies revealed the nature of the D:C mismatch by showing that D can form a wobble-type base pair with C. We then asked whether competition with G would decrease the mismatched primer extension. We performed nonenzymatic primer extension with all four activated nucleotides on randomized RNA templates containing all four letters and used deep sequencing to analyze the products. We found that the DUCG genetic system exhibited a more even product distribution and a lower mismatch frequency than the canonical AUCG system. Furthermore, primer extension is greatly reduced following all mismatches, including the D:C mismatch. Our study suggests that D deserves further attention for its possible role in the RNA World and as a potentially useful component of artificial nonenzymatic RNA replication systems.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗