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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 199 records · Page 11
All sourcesNASA NTRSDOE OSTI
NASA NTRS2023

Space Shuttle Program Dual Docked Operations

- Dual Docked Operations (DDO) is the docking or undocking of a Russian Vehicle (RV) during Space Shuttle Orbiter/International Space Station (ISS) mated operations. - This paper and presentation summarizes the concept definition, studies, and analysis results generated by the Space Shuttle Program (SSP), ISS Program (ISSP), and Mission Operations Directorate for implementing DDO during mated Orbiter/ISS missions. [1] - Due to the ever-increasing visiting vehicle traffic to and from the ISS, it became apparent to both the ISSP and the SSP that there would arise occasions where conflicts between a visiting vehicle docking and/or undocking could overlap with a planned Space Shuttle launch and/or during mated Orbiter/ISS operations. - This potential conflict provided the genesis for evaluating risk mitigations to gain maximum flexibility for managing potential visiting vehicle traffic to and from the ISS and to maximize launch and landing opportunities for all visiting vehicles. - Reviews were conducted to assess the viability and readiness of the SSP to protect for DDO on any given mission and it was found to be t echnically feasible

Launch vehicles↗
NASA NTRSDate not supplied

Artemis IV Docking in Radiation Belt Charging Environment

NASA’s Artemis IV mission is planned to deliver the International Habitation Module (I-Hab) to the Gateway space station in lunar orbit. The I-Hab will be launched aboard the Space Launch System (SLS) vehicle as a co-manifested payload with the Orion spacecraft. After translunar injection begins, the Orion spacecraft will separate from the SLS Exploration Upper Stage (EUS) and then dock with the I-Hab to extract it from the EUS. Because of the altitude, orientation, and time for this to occur, the vehicle-to-vehicle potential between the I-Hab/EUS vehicle and Orion spacecraft could exceed several thousand volts. The docking of these two spacecrafts with such large differential potentials presents a challenge for the vehicles. This presentation describes the space environments at the docking altitude, the calculated vehicle-to-vehicle potential, and the possible impacts of the resulting voltage and current transients occurring at first contact. Additionally, possible risk mitigation tests to demonstrate compatibility with the transient current and voltages will be presented.

Matthew Mccollum↗
DOE OSTI2020

Screening of Therapeutic Agents for COVID-19 Using Machine Learning and Ensemble Docking Studies

The current pandemic demands a search for therapeutic agents against the novel coronavirus SARS-CoV-2. In this work, we present an efficient computational strategy that combines machine learning (ML)-based models and high-fidelity ensemble docking studies to enable rapid screening of possible therapeutic ligands. Targeting the binding affinity of molecules for either the isolated SARS-CoV-2 S-protein at its host receptor region or the S-protein:human ACE2 interface complex, we screen ligands from drug and biomolecule data sets that can potentially limit and/or disrupt the host-virus interactions. Top scoring one hundred eighty-seven ligands (with 75 approved by the Food and Drug Administration) are further validated by all atom docking studies. Important molecular descriptors ( 2 χ n , topological surface area, and ring count) and promising chemical fragments (oxolane, hydroxy, and imidazole) are identified to guide future experiments. Overall, this work expands our knowledge of small-molecule treatment against COVID-19 and provides a general screening pathway (combining quick ML models with expensive high-fidelity simulations) for targeting several chemical/biochemical problems.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Likelihood-based signal and noise analysis for docking of models into cryo-EM maps

Fast, reliable docking of models into cryo-EM maps requires understanding of the errors in the maps and the models. Likelihood-based approaches to errors have proven to be powerful and adaptable in experimental structural biology, finding applications in both crystallography and cryo-EM. Indeed, previous crystallographic work on the errors in structural models is directly applicable to likelihood targets in cryo-EM. Likelihood targets in Fourier space are derived here to characterize, based on the comparison of half-maps, the direction- and resolution-dependent variation in the strength of both signal and noise in the data. Because the signal depends on local features, the signal and noise are analysed in local regions of the cryo-EM reconstruction. The likelihood analysis extends to prediction of the signal that will be achieved in any docking calculation for a model of specified quality and completeness. A related calculation generalizes a previous measure of the information gained by making the cryo-EM reconstruction.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Likelihood-based docking of models into cryo-EM maps

Optimized docking of models into cryo-EM maps requires exploiting an understanding of the signal expected in the data to minimize the calculation time while maintaining sufficient signal. The likelihood-based rotation function used in crystallography can be employed to establish plausible orientations in a docking search. A phased likelihood translation function yields scores for the placement and rigid-body refinement of oriented models. Optimized strategies for choices of the resolution of data from the cryo-EM maps to use in the calculations and the size of search volumes are based on expected log-likelihood-gain scores computed in advance of the search calculation. Tests demonstrate that the new procedure is fast, robust and effective at placing models into even challenging cryo-EM maps.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Likelihood-based interactive local docking into cryo-EM maps in ChimeraX

The interpretation of cryo-EM maps often includes the docking of known or predicted structures of the components, which is particularly useful when the map resolution is worse than 4 Å. Although it can be effective to search the entire map to find the best placement of a component, the process can be slow when the maps are large. However, frequently there is a well-founded hypothesis about where particular components are located. In such cases, a local search using a map subvolume will be much faster because the search volume is smaller, and more sensitive because optimizing the search volume for the rotation-search step enhances the signal to noise. A Fourier-space likelihood-based local search approach, based on the previously published em_placement software, has been implemented in the new emplace_local program. Tests confirm that the local search approach enhances the speed and sensitivity of the computations. An interactive graphical interface in the ChimeraX molecular-graphics program provides a convenient way to set up and evaluate docking calculations, particularly in defining the part of the map into which the components should be placed.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Fragment binding to the Nsp3 macrodomain of SARS-CoV-2 identified through crystallographic screening and computational docking

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) macrodomain within the nonstructural protein 3 counteracts host-mediated antiviral adenosine diphosphate–ribosylation signaling. This enzyme is a promising antiviral target because catalytic mutations render viruses nonpathogenic. Here, we report a massive crystallographic screening and computational docking effort, identifying new chemical matter primarily targeting the active site of the macrodomain. Crystallographic screening of 2533 diverse fragments resulted in 214 unique macrodomain-binders. An additional 60 molecules were selected from docking more than 20 million fragments, of which 20 were crystallographically confirmed. X-ray data collection to ultra-high resolution and at physiological temperature enabled assessment of the conformational heterogeneity around the active site. Several fragment hits were confirmed by solution binding using three biophysical techniques (differential scanning fluorimetry, homogeneous time-resolved fluorescence, and isothermal titration calorimetry). The 234 fragment structures explore a wide range of chemotypes and provide starting points for development of potent SARS-CoV-2 macrodomain inhibitors.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS1962

RENDEZVOUS AND DOCKING TECHNIQUES

To implement the primary space mission of this decade – manned lunar exploration -- the operational assistance of rendezvous and docking is being considered as an alternative to possible problems in obtaining a boost vehicle capable of direct flight. This paper concentrates on the mechanization of the rendezvous and docking phase of such a lunar mission. As indicated in previous papers, rendezvous can take place in either an earth or lunar orbit (or on the lunar surface); it can involve the mating of stages, transfer of fuel, or the return of a shuttle to a “mother” ship; direct ascent or parking orbits can be used; the orbits can be circular or more general ellipses; finally, either or both of the spacecraft can participate in the rendezvous maneuvers. Since there is no intent here to discuss the pros and cons of each approach or to cover all possible mission profiles, guidance schemes and hardware configurations, one particular profile has been selected to display the significant features of most rendezvous missions. In many respects, rendezvous is less difficult than aircraft interception since the target is friendly and there is no severe time constraint. The latter feature allows considerable freedom of design especially with the great versatility of a human in the loop. This remains true even for a purely automatic mode. Perhaps the largest design problem concerns the selection of the mission to be implemented followed by the optimization or systems engineering of a mechanization from the multitude of possible schemes and techniques. A most important factor in the optimization is that of reliability and the redundancy, alternate or backup modes, etc., associated with the approach. While a primary system can be rather easily mechanized with modest equipment requirements, reliability considerations will result in additional hardware, tighter specifications and more safety factors (e. g., propellant margin). This is a very complex area and will only briefly be mentioned in the following discussion.

Rendezvous↗
NASA NTRS2018

Capture Latch Assembly for the NASA Docking System

Final Paper and not the abstract is attached. a summary of the Design, Development, and Qualification of the Capture Latch Assembly (CLA) for the NASA Docking System Block 1 (NDSB1). The CLA is an integral part of the Soft Capture System (SCS) of the NDSB1, serving the purpose of connecting the mating SCS Rings of two docking vehicles. The paper will present an overview of the function of the CLA and its basic concept of operations, including a summary of the major components of the CLA. The development, qualification, and production of the CLA will then be described. Particular focus will be provided on two major issues that occurred during production and qualification of the CLA. The first issue was failures of the CLA Motor (CLM) during acceptance testing (AT). The failures of the CLM were ultimately determined to be due to design defects and manufacturing errors in the motor commutation sensor assembly. The second issue was failure of the secondary release mechanism, or Contingency Capture Latch Release (CCLR) mechanism during development and qualification testing. The CCLR failures were found to be a result of excess free play in the release mechanism, resulting in wear leading to galling inside the release mechanism. An overview of each failure will be provided, along with a summary of the failure investigation and recovery process. Finally, Lessons Learned from each of the major issues and the overall development of the Capture Latch will be presented.

Capture Latch↗
NASA NTRSDate not supplied

Modeling of a Stewart Platform for Analyzing One Directional Dynamics for Spacecraft Docking Operations

A one-directional dynamic model of a Stewart Platform was developed to assist NASA in analyzing the dynamic response in spacecraft docking operations. A simplified mechanical drawing was created, capturing the physical structure's main features. A simplified schematic diagram was developed in a lumped mass model from the mechanical drawing. Three differential equations were derived according to the schematic diagram. A Simulink diagram was created using MATLAB to represent the three equations. System parameters, including spring constants and masses, are derived in detail from the physical system. The model can be used for further analysis via computer simulation in predicting dynamic response in its main docking direction, i.e., up-and-down motion.

Stewart Platform↗
DOE OSTI2019

Nano Sb{sub 2}O{sub 3} catalyzed green synthesis, cytotoxic activity, and molecular docking study of novel α-aminophosphonates

Green synthesis of a series of novel dialkyl (aryl substituted)(2-fluoro-4-((2-methylcarbamoyl)pyridine-4-yl)oxy)phenyl)amino)methyl)phosphonates is accomplished by a simple and an efficient one pot three component reaction of 3-(4-amino-3-fluorobenzyl)-N-methylbenzamide with different substituted aromatic aldehydes and dialkyl phosphite in the presence of nano Sb{sub 2}O{sub 3} catalyst under solvent free conditions at 40–50 °C to obtain the title compounds. Excellent isolated product yields are obtained (85–95%) with high purity within shorter reaction times (30–60 min). The title compounds are characterized by IR, {sup 1}H, {sup 13}C, {sup 31}P-NMR and mass spectral data. The synthesized compounds are screened for their anticell-proliferation activity on seven cell lines, Control cells–HEK293 (human embryonic kidney), DU-145 (human prostate adenocarcinoma), MCF-7 (human ER+/PR+/Her2− breast cancer), MDA-MB-231 (human ER−/PR−/Her2− breast cancer), Mia-Paca-2 (human pancreatic carcinoma), HeLa (human cervical cancer) cells as well as HepG2 (human hepatocellular carcinoma) cancer cell lines using Sulforhodamine B (SRB) assay method. Docking studies were carried out for all these synthesized compounds against topoisomerase-II by using Auto dock method. Doxorubicin was taken as standard. Compounds 4a, 4c, 4d, 4e, 4h, 4i, 4k, and 4l exhibited higher cytotoxic activity than the standard doxorubicin. .

60 APPLIED LIFE SCIENCES↗
DOE OSTI2019

Synthesis, in vitro antifungal evaluation and docking studies of novel derivatives of imidazoles and benzimidazoles

A series of imidazole and benzimidazole derivatives was designed and prepared in good yields via convenient and efficient two steps synthetic route using readily available starting materials. The structures of the synthesized compounds and their intermediates were characterized by IR, {sup 1}H-NMR, {sup 13}C-NMR spectroscopy, and MS spectra. The in vitro antifungal activities of the targeted compounds were evaluated against Candida Albicans, Cryptococcus neoformans, Aspergillus niger, and Microsporum gypseum. The results showed that some of these azole-derivatives exhibited good to excellent antifungal activities against the used strains especially C. neoformans and A. niger. For example, compound 6b, 1-[2-Phenyl-2-(3-phenyl-propoxy)-ethyl]-1H-imidazole, was quite effective on the C. neoformans, A. niger, and M. gypseum with MIC 1.95 µg mL{sup −1}. The in silico molecular docking study was also done on the synthesized compounds and the results showed they have minimum binding energy and relatively good affinity toward cytochrome P450. According to the in vitro antifungal results and molecular docking studies, the compounds 6a–d can be selected as lead compounds for further pharmaceutical investigations.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2019

Fluorophenols bearing nitrogenated heterocycle moieties, a class of novel Keap1-Nrf2 protein-protein interaction inhibitors: synthesis, antioxidant stress screening and molecular docking

In the present study, we introduced the nitrogenated heterocycles and fluorine atoms into the 2,5′-dibromo-4,5,2′-trihydroxyl diphenylmethanone (LM49), a bromophenol analog previously reported for its strong antioxidant ability involving in the Keap1–Nrf2 pathway. Twenty-seven fluorophenols 6a–6g, 8a–8k, 10a–10g, and 12a–12b were prepared, evaluated for their antioxidant activity in EA.hy926 cells, and investigated their interacted approach and probable mode of action with key protein Keap1 by molecular docking. Fluorophenols 6f, 8d, 8f, 8h, and 8i with EC{sub 50} values ranging from 0.82 to 6.71 µM were found to be more active compared with the standard control quercetin (EC{sub 50} = 18 µM). Among them, compound 8h with an EC{sub 50} value of 0.82 µM showed the identical activity to lead compound LM49 (EC{sub 50} = 0.7 µM). Moreover, the preferable water solubility and forming salt possibility of 8h contribute to its druggability. Further molecular docking of the optimal compound 8h with key protein Keap1 indicated that 8h stably bonded to the receptor protein by the formation of hydrogen bonds, the conjugated six-membered ring was close to the key residue Arg-415 attached to the Nrf2 on Keap1-Kelch, affecting its properties, and the change leaded to the dissociation of Nrf2 from the junction with Keap1-Kelch into the nucleus exerting its antioxidant protective effect. This study introduced a class of fluorophenols containing nitrogenated heterocycles for the development of novel Keap1-Nrf2 protein–protein interaction (PPI) inhibitors. Keap1-Kelch is suggested the most potential target protein for such class of halophenols.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2019

Design, synthesis, molecular docking, antimicrobial, and antioxidant activities of new phenylsulfamoyl carboxylic acids of pharmacological interest

Abstracts: The research explores the facile synthesis of some new phenylsulfamoyl carboxylic acids, their molecular docking, antimicrobial, and antioxidant activities. The procedure involved the mild reaction of amino acids with benzenesulfonyl chloride in a medium of aqueous base. The compounds were characterized using FTIR, {sup 1}H-NMR, {sup 13}C-NMR, and an elemental analysis. They were tested for their antimicrobial activities against Staphylococcus aureus, Escherichia coli, Bacillus subtilis, Pseudomonas aeruginosa, Salmonella typhi, Candida albicans, and Aspergillus niger microorganisms. The antioxidant activity of the compounds were measured in vitro by the inhibition of generated stable 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical. The molecular docking was carried out properly and five different disease conditions were studied, namely: trypanosomiasis, malaria, bacterial, fungal infections, and oxidative stress. From the results, compounds 4c, 4d, 4e, and 4g possess more excellent in vitro antibacterial and antifungal activities than the standard drug Ofloxacin used. Compound 4e displayed the most excellent antioxidant activity. Compound 4g showed significant 2D interaction with amino acid residue of urate oxidase from Aspergillus flavus complexed with uracil. Interestingly, compounds 4a, 4c, 4d, 4e, and 4g exhibited excellent antibacterial, antifungal, antioxidant, antitrypanosome, and antimalaria activities comparable to the corresponding standard drugs such as Penicillin, Ketoconazole; α-Tocopherol, Melarsoprol, and Chloroquine respectively. All the compounds were confirmed drug-like according to “Lipinski’s rule of five”. The compounds were found to be promising antibacterial, antifungal, antioxidant, and antitrypanosome agents.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2025

Host cell and viral protease targets of human SERPINs identified by in silico docking

Serine protease inhibitors (SERPINs) are involved in various physiological processes and diseases, such as inflammation, cancer metastasis, and neurodegeneration. Their role in viral infections is poorly understood, as their expression patterns during infection and the range of proteases they target have yet to be fully characterized. Here, we show widespread expression of human SERPINs in response to respiratory virus infections, both in bronchioalveolar lavages from COVID-19 patients and in polarized human airway epithelial cultures. Using in silico docking of 10 SERPINs to 48 host proteases, we confirm known targets and predict new interactions. Protease activity assays validated selected interactions, confirming the newly predicted host targets for PAI-1 (SERPINE1) and PAI-2 (SERPINB2). PAI-1 inhibits cathepsin L, essential for SARS-CoV-2 maturation, and suppresses multi-cycle replication of both ancestral SARS-CoV-2 WA-1 and its variant Omicron BA.1. In addition, we identify PAI-2 as an antiviral SERPIN that reduces infectivity of human adenovirus 5 by directly inhibiting the adenoviral protease. Our study leverages in silico docking using full-length 3D protein structures to uncover new SERPIN targets, offering a range of candidate targets for therapeutic interventions.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2019

Molecular docking predictions of fragrance binding to human leukocyte antigen molecules

Abstract Background Over 4000 small chemicals have been identified as allergens capable of inducing skin sensitization. Many sensitizers are hypothesized to act as haptens producing novel antigens, which can be presented to T cells by human leukocyte antigens (HLAs). Recent studies suggest that some chemical allergens use hapten‐independent mechanisms. Objective To determine whether molecular docking can identify HLA molecules that bind skin‐sensitizing chemical allergens. Methods Structural models of HLA molecules were used as the basis for molecular docking of 22 chemical allergens. Allergens predicted to bind HLA‐B*57:01 were tested for their ability to stimulate T cells by the use of proliferation and interferon‐gamma enzyme‐linked immunospot assays. Results Chemical allergens that did not satisfy the criteria for hapten activity in vitro were predicted to bind more strongly to common HLA isoforms than those with known hapten activity. HLA‐B*57:01, which is an HLA allele required for drug hypersensitivity reactions, was predicted to bind several allergens, including benzyl benzoate, benzyl cinnamate, and benzyl salicylate. In in vitro T cell stimulation assays, benzyl salicylate and benzyl cinnamate were found to stimulate T cell responses from HLA‐B*57:01 carriers. Conclusions These data suggest that small‐molecule skin sensitizers have the potential to interact with HLA, and show that T cell‐based in vitro assays may be used to evaluate the immunogenicity of skin‐sensitizing chemicals.

Schutte, Ryan J.↗