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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 667 records · Page 37
All sourcesNASA NTRSDOE OSTI
NASA NTRSDate not supplied

Options for Offloading a 90-Ton Common Habitat from its Lander on the Surface of Mars

The Common Habitat is a large, long-duration habitat being explored as part of a conceptual study (not an active NASA program) that uses an SLS core stage liquid oxygen (LOX) tank as its primary structure. Measuring 8.4 meters in diameter and 15.6 meters in length, it is manufactured as a habitat and launched as such into space. It is intended for use on the Moon as part of a permanently occupied outpost, on Mars as part of an outpost that will be occupied for hundreds of days at a time, and in deep space as part of the Deep Space Exploration Vehicle where it will support crewed missions up to 1200 days in duration. A study of internal orientation and crew size resulted in a Common Habitat configuration sized for a crew of eight with a three-deck horizontal orientation. There are obvious challenges associated with the delivery of such a large habitat, which may mass as much as 90-tons when initially deployed. The Mars destination in particular imposes extreme challenges due to Martian gravity. This paper identifies initial options for the offloading of a 90-ton Common Habitat from a lander spacecraft on the surface of Mars. On Mars, the Common Habitat is part of a surface outpost where a Habitation Zone includes the Common Habitat docked to a two-chamber airlock node, up to two logistics modules, and up to two pressurized rovers. It is connected by underground conduit to a radiator farm and communications tower assembly. These elements and other surface infrastructure, including robotic systems for surface preparation, are landed prior to the Common Habitat. In the baseline Common Habitat Architecture, the Common Habitat is delivered on the third heavy cargo flight. The Habitation Zone configuration dictates that the Common Habitat needs to be offloaded from the lander. All of the docked elements require direct access to the surface and the Common Habitat must actually be placed in a trench to lower its docking ports to be level with those of the mated elements. Additionally, the habitat must be emplaced in a horizontal configuration, while for any conceivable Earth launch system it must be launched in a vertical configuration. It is true that the Common Habitat must be offloaded from its lander on both the Moon and Mars and a common offloading system must therefore work in both destinations. Mars, however, is considered the driving case for offloading in most, but not all, aspects. A four-day internal study in 2021 recommended that a modified Starship be used to land the Common Habitat on Mars and considered multiple approaches to offload the Common Habitat from the payload section and lower it to the surface. The topic was presented at a public hackathon organized by the Johnson Space Center’s Emerge Employee Resource Group. One team took on the challenge and proposed a concept in some ways similar to the previously considered jib crane. Despite the excellent innovation in the team’s work, a number of study refinements are necessary to truly establish feasibility. These and other future work needed to mature the concept are discussed in this work.

Lander Offloading↗
NASA NTRSDate not supplied

Towards Plume Impingement Modeling in Space Environments

After 30 years human presence in low-earth orbit, NASA is returning to the moon and eventually will go to Mars. To this end, NASA is constructing the Lunar Gateway, an ISS-like space station to act as a home base for Lunar exploration. A large space station must be assembled while in orbit, using a “piecemeal” approach. In this context, it means that the different modules will arrive at different times and attach to what is already in service. The ISS provides an excellent example of this approach, and the proposed Lunar Gateway will undergo a similar assembly process. This assembly is achieved via “docking” maneuvers between modules, which are made possible by sequential firings of the onboard reaction control system (RCS) thrusters. They work by firing hot gases to produce adverse thrust and the needed change in velocity to safely finish the docking approach. The issue is that the gas from these thrusters' forms flow structures described as “plumes” and can impinge onto the outer surfaces of the space station, causing unwanted forces and moments, heat loads, sediment deposition, and in extreme cases, even surface erosion. All mechanisms that can damage the space station and must be avoided. Both permanent and visiting modules will have these RCS thruster exhaust impingement problems. Accurately and efficiently modeling these plume is an involved multi-physics calculation but also an important tool when designing the control algorithms of approaching modules. This poster presents progress towards this simulation on two fronts. First is the verification of OpenFOAM for rarefied plume impingement calculations by direct comparison to published DAC cases. Second is the estimation of plume impingement strikes over the time scale of an entire docking event. This is done by using a simple plume source flow model and a prescribed motion visualizer—coded in Python. Together these tools help push NASA's capabilities for simulating these plume impingement effects.

Rarefied Flows↗
DOE OSTI2019

Identification of Ebola Virus Inhibitors Targeting GP2 Using Principles of Molecular Mimicry

A key step in the Ebola virus (EBOV) replication cycle involves conformational changes in viral glycoprotein 2 (GP2) which facilitate host-viral membrane fusion and subsequent release of the viral genome. Ebola GP2 plays a critical role in virus entry and has similarities in mechanism and structure to the HIV gp41 protein for which inhibitors have been successfully developed. In this work, a putative binding pocket for the C-terminal heptad repeat in the N-terminal heptad repeat trimer was targeted for identification of small molecules that arrest EBOV-host membrane fusion. Two computational structure-based virtual screens of ~1.7 M compounds were performed (DOCK program) against a GP2 five-helix bundle, resulting in 165 commercially available compounds purchased for experimental testing. Based on assessment of inhibitory activity, cytotoxicity, and target specificity, four promising candidates emerged with 50% inhibitory concentration values in the 3 to 26 μM range. Molecular dynamics simulations of the two most potent candidates in their DOCK-predicted binding poses indicate that the majority of favorable interactions involve seven highly conserved residues that can be used to guide further inhibitor development and refinement targeting EBOV. The most recent Ebola virus disease outbreak, from 2014 to 2016, resulted in approximately 28,000 individuals becoming infected, which led to over 12,000 causalities worldwide. The particularly high pathogenicity of the virus makes paramount the identification and development of promising lead compounds to serve as inhibitors of Ebola infection. To limit viral load, the virus-host membrane fusion event can be targeted through the inhibition of the class I fusion glycoprotein of. In the current work, several promising small-molecule inhibitors that target the glycoprotein GP2 were identified through systematic application of structure-based computational and experimental drug design procedures.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2015

Computational Enzymology and Organophosphorus Degrading Enzymes: Promising Approaches Toward Remediation Technologies of Warfare Agents and Pesticides

The re-emergence of chemical weapons as a global threat in hands of terrorist groups, together with an increasing number of pesticides intoxications and environmental contaminations worldwide, has called the attention of the scientific community for the need of improvement in the technologies for detoxification of organophosphorus (OP) compounds. A compelling strategy is the use of bioremediation by enzymes that are able to hydrolyze these molecules to harmless chemical species. Several enzymes have been studied and engineered for this purpose. However, their mechanisms of action are not well understood. Theoretical investigations may help elucidate important aspects of these mechanisms and help in the development of more efficient bio-remediators. In this review, we point out the major contributions of computational methodologies applied to enzyme based detoxification of OPs. Furthermore, we highlight the use of PTE, PON, DFP, and BuChE as enzymes used in OP detoxification process and how computational tools such as molecular docking, molecular dynamics simulations and combined quantum mechanical/molecular mechanics have and will continue to contribute to this very important area of research.The re-emergence of chemical weapons as a global threat in hands of terrorist groups, together with an increasing number of pesticides intoxications and environmental contaminations worldwide, has called the attention of the scientific community for the need of improvement in the technologies for detoxification of organophosphorus (OP) compounds. A compelling strategy is the use of bioremediation by enzymes that are able to hydrolyze these molecules to harmless chemical species. Several enzymes have been studied and engineered for this purpose. However, their mechanisms of action are not well understood. Theoretical investigations may help elucidate important aspects of these mechanisms and help in the development of more efficient bio-remediators. In this review, we point out the major contributions of computational methodologies applied to enzyme based detoxification of OPs. Furthermore, we highlight the use of PTE, PON, DFP, and BuChE as enzymes used in OP detoxification process and how computational tools such as molecular docking, molecular dynamics simulations and combined quantum mechanical/molecular mechanics have and will continue to contribute to this very important area of research.

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

A goldilocks computational protocol for inhibitor discovery targeting DNA damage responses including replication-repair functions

While many researchers can design knockdown and knockout methodologies to remove a gene product, this is mainly untrue for new chemical inhibitor designs that empower multifunctional DNA Damage Response (DDR) networks. Here, we present a robust Goldilocks (GL) computational discovery protocol to efficiently innovate inhibitor tools and preclinical drug candidates for cellular and structural biologists without requiring extensive virtual screen (VS) and chemical synthesis expertise. By computationally targeting DDR replication and repair proteins, we exemplify the identification of DDR target sites and compounds to probe cancer biology. Our GL pipeline integrates experimental and predicted structures to efficiently discover leads, allowing early-structure and early-testing (ESET) experiments by many laboratories. By employing an efficient VS protocol to examine protein-protein interfaces (PPIs) and allosteric interactions, we identify ligand binding sites beyond active sites, leveraging in silico advances for molecular docking and modeling to screen PPIs and multiple targets. A diverse 3,174 compound ESET library combines Diamond Light Source DSI-poised, Protein Data Bank fragments, and FDA-approved drugs to span relevant chemotypes and facilitate downstream hit evaluation efficiency for academic laboratories. Two VS per library and multiple ranked ligand binding poses enable target testing for several DDR targets. This GL library and protocol can thus strategically probe multiple DDR network targets and identify readily available compounds for early structural and activity testing to overcome bottlenecks that can limit timely breakthrough drug discoveries. By testing accessible compounds to dissect multi-functional DDRs and suggesting inhibitor mechanisms from initial docking, the GL approach may enable more groups to help accelerate discovery, suggest new sites and compounds for challenging targets including emerging biothreats and advance cancer biology for future precision medicine clinical trials.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Structure-Based Design of Small-Molecule Inhibitors of Human Interleukin-6

Human Interleukin-6 (hIL-6) is a pro inflammatory cytokine that binds to its receptor, IL-6Rα followed by binding to gp130 and subsequent dimerization to form a hexamer signaling complex. As a critical inflammation mediator, hIL-6 is associated with a diverse range of diseases and monoclonal antibodies in clinical use that either target IL-6Rα or hIL-6 to inhibit signaling. Here, we perform high-throughput structure-based computational screening using ensemble docking for small-molecule antagonists for which the target conformations were taken from 600 ns long molecular dynamics simulations of the apo protein. Prior knowledge of the contact sites from binary complex studies and experimental work was incorporated into the docking studies. The top 20 scoring ligands from the in silico studies after post analysis were subjected to in vitro functional assays. Among these compounds, the ligand with the second-highest calculated binding affinity experimentally showed an ~84% inhibitory effect on IL6-induced STAT3 reporter activity at 10 μM concentration. This finding may pave the way for designing small-molecule inhibitors of hIL-6 of therapeutic significance.

Human Interleukin-6↗
NASA NTRS2016

Navigation and Alignment Aids Concept of Operations and Supplemental Design Information

The IDSS Navigation and Alignment Aids Concept of Operations and Supplemental Design Information document provides supplemental information to the IDSS IDD. The guide provides insight into the navigation and alignment aids design, and how those aids can be utilized by incoming vehicles for proximity operations and docking. The navigation aids are paramount to successful docking.

International Docking Standard Target↗
NASA NTRS2020

Electric Six Degree of Freedom Installation Timelapse (Six Degree of Freedom Dynamic Test System)

The Six-degree-of-freedom Dynamic Test System (SDTS) is a short-range real-time motion based testing platform. Its primary use at NASA/JSC has been for development and qualification testing of docking systems, robotic assisted berthing mechanisms, and dynamic attachment systems. The SDTS is a closed-loop force feedback system that can simulate on-orbit contact dynamics between two vehicles utilizing the actual mechanical interfaces for testing. The facility is controlled by interconnected computers running real-time simulation software that takes measured contact forces, integrates the equations of motion in real time, and provide those states back into the motion table. This infrastructure can also be used for non-mating applications such as relative position sensor testing/evaluations. The SDTS facility provides a superstructure for mounting test articles, multiple test sensors, an intercom network for voice communications, and a synchronized timing system for data acquisition that includes HD video. This time-lapse video shows the buildup and testing of a modern electric actuation system created by Mikrolar, Inc. at the Johnson Space Center. This motion base will replace the current hydraulic actuator system, which is been in use since the 1970s, for all-future NASA testing. Once the system goes through customization to provide JSC’s unique closed-loop environment, the facility will help certify docking system and attach mechanisms on the ground before we send the first woman and the next man to the lunar surface

hexapod↗
NASA NTRSDate not supplied

Design, Development, and Test of the Advanced Apollo Orbital Assembly System

As spaceflight moves toward commercial solutions for Crew Vehicles and Space Stations, opportunity exists to lower costs with novel designs. Probe and cone docking systems provide a lightweight, low cost, and high-performance docking solution. This work revisits the Apollo probe and cone design and modifies it for the requirements of today’s computer-controlled spacecraft. This new system is called the Advanced Apollo Orbital Assembly (APOA) system, and is intended to support satellite, cargo, and space station assembly missions. A simulation of the APOA was programmed, components were sized, and a design was created by scaling the probe to the size of an EELV Secondary Payload Adapter (ESPA) tunnel. Prototype test hardware was 3D printed using Fused Deposition Modeling (FDM) methods with Polylactic Acid (PLA) material. Testing of the APOA-ESPA was conducted at Marshall Space Flight Center’s (MSFC) Flat Floor, and a test-correlated simulation is used to evaluate a Monte-Carlo of Initial Contact Conditions (ICC’s) to establish baseline performance. The successful development, test, and correlation of the APOA-ESPA proves the design validity and increases Technology Readiness Level (TRL) from 2 to 4. This work opens the door to construction of an APOA-ESPA from flight like materials, and to develop a larger scale prototype APOA. When the full scale APOA is incorporated with the Common Berthing Mechanism (CBM), becomes the Hybrid Berthing System (HBS), which allows for berthing without a robotic arm.

Berthing↗
DOE OSTI2016

PB-AM: An open-source, fully analytical linear poisson-boltzmann solver

Here, we present the open source distributed software package Poisson-Boltzmann Analytical Method (PB-AM), a fully analytical solution to the linearized PB equation, for molecules represented as non-overlapping spherical cavities. The PB-AM software package includes the generation of outputs files appropriate for visualization using visual molecular dynamics, a Brownian dynamics scheme that uses periodic boundary conditions to simulate dynamics, the ability to specify docking criteria, and offers two different kinetics schemes to evaluate biomolecular association rate constants. Given that PB-AM defines mutual polarization completely and accurately, it can be refactored as a many-body expansion to explore 2- and 3-body polarization. Additionally, the software has been integrated into the Adaptive Poisson-Boltzmann Solver (APBS) software package to make it more accessible to a larger group of scientists, educators, and students that are more familiar with the APBS framework.

97 MATHEMATICS AND COMPUTING↗
DOE OSTI2025

An evolutionarily conserved tryptophan cage promotes folding of the extended RNA recognition motif in the hnRNPR ‐like protein family

Abstract The heterogeneous nuclear ribonucleoprotein (hnRNP) R‐like family is a class of RNA binding proteins in the hnRNP superfamily with diverse functions in RNA processing. Here, we present the 1.90 Å X‐ray crystal structure and solution NMR studies of the first RNA recognition motif (RRM) of human hnRNPR. We find that this domain adopts an extended RRM (eRRM1) featuring a canonical RRM with a structured N‐terminal extension (N ext ) motif that docks against the RRM and extends the β‐sheet surface. The adjoining loop is structured and forms a tryptophan cage motif to position the N ext motif for docking to the RRM. Combining mutagenesis, solution NMR spectroscopy, and thermal denaturation studies, we evaluate the importance of residues in the N ext –RRM interface and adjoining loop on eRRM folding and conformational dynamics. We find that these sites are essential for protein solubility, conformational ordering, and thermal stability. Consistent with their importance, mutations in the N ext –RRM interface and loop are associated with several cancers in a survey of somatic mutations in cancer studies. Sequence and structure comparison of the human hnRNPR eRRM1 to experimentally verified and predicted hnRNPR‐like proteins reveals conserved features in the eRRM.

Biochemistry & Molecular Biology↗
DOE OSTI2020

Machine learning-based prediction of enzyme substrate scope: Application to bacterial nitrilases

Predicting the range of substrates accepted by an enzyme from its amino acid sequence is challenging. Although sequenc- and structure-based annotation approaches are often accurate for predicting broad categories of substrate specificity, they generally cannot predict which specific molecules will be accepted as substrates for a given enzyme, particularly within a class of closely related molecules. Combining targeted experimental activity data with structural modeling, ligand docking, and physicochemical properties of proteins and ligands with various machine learning models provides complementary information that can lead to accurate predictions of substrate scope for related enzymes. Here we describe such an approach that can predict the substrate scope of bacterial nitrilases, which catalyze the hydrolysis of nitrile compounds to the corresponding carboxylic acids and ammonia. Each of the four machine learning models (logistic regression, random forest, gradient-boosted decision trees, and support vector machines) performed similarly (average ROC = 0.9, average accuracy = ~82%) for predicting substrate scope for this dataset, although random forest offers some advantages. Finally, this approach is intended to be highly modular with respect to physicochemical property calculations and software used for structural modeling and docking.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2015

Novel insights into the apoptosis mechanism of DNA topoisomerase I inhibitor isoliquiritigenin on HCC tumor cell

The inhibitory effect of DNA topoisomerase (Top I) by isoliquiritigenin(ISO) were investigated and their interaction mechanism was evaluated using methods including UV–vis absorption, fluorescence, coupled with molecular simulation, and using the MTT method of inhibition rate of HCC tumor cell SNU475 proliferation assay, finally, the interaction of ISO with calf thymus DNA was investigated by melting measurements and molecular docking studies. It was found that isoliquiritigenin reversibly inhibited DNA Top I in a competitive manner with the concentrations of ISO resulting in 50% activity lost (IC{sub 50}) were estimated to be 0.178 ± 0.12 mM. Isoliquiritigenin exhibited a strong ability to quench the intrinsic fluorescence of Top I through a static quenching procedure. The positive values of enthalpy change and entropy change suggested that the binding of isoliquiritigenin to Top I was driven mainly by hydrophobic interactions. The molecular docking results revealed isoliquiritigenin actually interacted with the primary amino acid residues on the active site of Top I, and the detection results of fluorescence staining and the inhibitory effect on the growth of HCC SUN475 showed that isoliquiritigenin induced the apoptosis cells increased gradually. The interaction of ISO with DNA can cause the denaturation temperature to be increased, which indicated that the stabilization of the DNA helix was increased in the presence of ISO, which indicated that the results provide strong evidence for intercalative binding of ISO with DNA. - Highlights: • ISO reversibly inhibits TOP I activity in an A dose dependent manner. • Hydrophobic interactions play a major role in ISO–TOP I interaction. • ISO has a high affinity close to the active site pocket of TOP I. • The binding of ISO to DNA induces the stability of the structure of DNA.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Logical design of anti-prion agents using NAGARA

To accelerate the logical drug design procedure, we created the program “NAGARA,” a plugin for PyMOL, and applied it to the discovery of small compounds called medical chaperones (MCs) that stabilize the cellular form of a prion protein (PrP{sup C}). In NAGARA, we constructed a single platform to unify the docking simulation (DS), free energy calculation by molecular dynamics (MD) simulation, and interfragment interaction energy (IFIE) calculation by quantum chemistry (QC) calculation. NAGARA also enables large-scale parallel computing via a convenient graphical user interface. Here, we demonstrated its performance and its broad applicability from drug discovery to lead optimization with full compatibility with various experimental methods including Western blotting (WB) analysis, surface plasmon resonance (SPR), and nuclear magnetic resonance (NMR) measurements. Combining DS and WB, we discovered anti-prion activities for two compounds and tegobuvir (TGV), a non-nucleoside non-structural protein NS5B polymerase inhibitor showing activity against hepatitis C virus genotype 1. Binding profiles predicted by MD and QC are consistent with those obtained by SPR and NMR. Free energy analyses showed that these compounds stabilize the PrP{sup C} conformation by decreasing the conformational fluctuation of the PrP{sup C}. Because TGV has been already approved as a medicine, its extension to prion diseases is straightforward. Finally, we evaluated the affinities of the fragmented regions of TGV using QC and found a clue for its further optimization. By repeating WB, MD, and QC recursively, we were able to obtain the optimum lead structure. - Highlights: • NAGARA integrates docking simulation, molecular dynamics, and quantum chemistry. • We found many compounds, e.g., tegobuvir (TGV), that exhibit anti-prion activities. • We obtained insights into the action mechanism of TGV as a medical chaperone. • Using QC, we obtained useful information for optimization of the lead compound, TGV. • NAGARA is a convenient platform for drug discovery and lead optimization.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Dissection of the angle of single fluorophore attached to the nucleotide in corkscrewing microtubules

Direct dissection of the angles of single fluorophores under an optical microscope has been a challenging approach to study the dynamics of proteins in an aqueous solution. For angle quantifications of single substrates, however, there was only one report (Nishizaka et al., 2014) because of difficulties of construction of experimental systems with active proteins working at the single-molecule level. We here show precise estimation of orientation of single fluorescent nucleotides bound to single tubulins that comprise microtubule. When single-headed kinesins immobilized on a glass surface drive the sliding of microtubules, microtubules show corkscrewing with regular pitches (Yajima et al., 2005 & 2008). We found, by using a three-dimensional tracking microscope, that S8A mutant kinesin also showed precise corkscrewing with a 330-nm pitch, which is 13% longer than that of the wild type. The assay with the mutant was combined with a defocused imaging technique to visualize the rotational behavior of fluorescent nucleotide bound to corkscrewing microtubule. Notably, the defocused pattern of single TAMRA-GTP periodically changed, precisely correlating to its precession movement. The time course of the change in the fluorophore angle projected to the xy-plane enabled to estimate both the fluorophore orientation against microtubule axis and the precision of angle-determination of analyses system. The orientation showed main distribution with peaks at∼40°, 50° and 60°. To identify their molecular conformations, the rigorous docking simulations were performed using an atomic-level structure modeled by fitting x-ray crystal structures to the cryo-electron microscopy map. Among isomers, 2′-O-EDA-GDP labeled with 5- or 6-TAMRA were mainly specified as possible candidates as a substrate, which suggested the hydrolysis of TAMRA-GTP by tubulins. - Highlights: • The mutant of single-headed kinesin drives the corkscrewing of microtubules with a longer pitch. • Orientation of single fluorescent GTP on rotating microtubule was measured by defocused imaging. • The orientation showed the distribution with peaks at∼40°, 50° and 60° against microtubule axis. • Docking simulation reveals possible molecular conformations and state of nucleotide on tubulin.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Sublethal doses of neonicotinoid imidacloprid can interact with honey bee chemosensory protein 1 (CSP1) and inhibit its function

As a frequently used neonicotinoid insecticide, imidacloprid can impair the chemoreceptive behavior of honey bees even at sublethal doses, while the physiochemical mechanism has not been further revealed. Here, multiple fluorescence spectra, thermodynamic method, and molecular docking were used to study the interaction and the functional inhibition of imidacloprid to the recombinant CSP1 protein in Asian honey bee, Apis cerana. The results showed that the fluorescence intensity (λ{sub em} = 332 nm) of CSP1 could be significantly quenched by imidacloprid in a dynamic mode. During the quenching process, ΔH > 0, ΔS > 0, indicating that the acting forces of imidacloprid with CSP1 are mainly hydrophobic interactions. Synchronous fluorescence showed that the fluorescence of CSP1 was mainly derived from tryptophan, and the hydrophobicity of tryptophan decreased with the increase of imidacloprid concentration. Molecular docking predicted the optimal pose and the amino acid composition of the binding process. Circular dichroism (CD) spectra showed that imidacloprid reduced the α-helix of CSP1 and caused the extension of the CSP1 peptide chain. In addition, the binding of CSP1 to floral scent β-ionone was inhibited by nearly 50% of the apparent association constant (K{sub A}) in the presence of 0.28–2.53 ng/bee of imidacloprid, and the inhibition rate of nearly 95% at 3.75 ng/bee of imidacloprid at sublethal dose level. This study initially revealed the molecular physiochemical mechanism that sublethal doses of neonicotinoid still interact and inhibit the physiological function of the honey bees' chemoreceptive system. - Highlights: • Sublethal doses of imidacloprid can directly interact with CSP1 in Apis cerana. • Sublethal imidacloprid can inhibit the function of CSP1 binding to semiochemicals. • The fluorescence intensity of CSP1 quenched by imidacloprid in a dynamic mode. • The binding between CSP1 and imidacloprid are driven by hydrophobic interactions. • Imidacloprid caused the extension of the CSP1 peptide chain.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

DOK1/PPARgamma pathway mediates anti-tumor ability of all-trans retinoic acid in breast cancer MCF-7 cells

Previous studies have showed the anticancer effect of the all-trans retinoic acid (ATRA) in many tumors including breast cancer; however, the underlying molecular mechanism is still poorly understood. This study experimentally revealed that ATRA treatment inhibited MCF-7 cell proliferation and promoted its apoptosis, along with an enhanced expression of docking protein 1 (DOK1). ATRA's effects on cell proliferation and apoptosis were prevented by DOK1 knockdown. In addition, the genetic silence of DOK1 can inhibit PPARγ expression and its activity. Moreover, inactivation of PPARγ by its specific inhibitor GW9662 reversed the impacts of ATRA on cell proliferation and apoptosis. Taken together, these results indicate that ATRA-enhanced expression of DOK1 activates PPARγ leading to inhibition of cell proliferation and enhancement of cell apoptosis in MCF-7 cell. - Highlights: • ATRA treatment inhibited MCF-7 cell proliferation, along with an enhanced expression of docking protein 1 (DOK1). • The genetic silence of DOK1 can inhibit PPARγ expression and its activity. • Inactivation of PPARγ by its specific inhibitor GW9662 reversed the impacts of ATRA on cell proliferation. • ATRA-enhanced expression of DOK1 activates PPARγ leading to inhibition of cell proliferation in MCF-7 cells.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Functional and structural characterization of a β-glucosidase involved in saponin metabolism from intestinal bacteria

Highlights: • Bifidobacterium longum are involved in the metabolism of saponins. • BlBG3 shows higher efficiency to saponins than known bacterial β-glucosidases. • First structure of β-glucosidase from intestinal bacteria to hydrolyze saponins. • A special binding pocket differs to other structural available GH3 β-glucosidases. • Molecular docking revealed the binding interactions of substrate with BlBG3. Saponins are natural glycosides widely used in medicine and the food industry. Although saponin metabolism in human is dependent on intestinal microbes, few involving bacteria enzymes have been identified. We cloned BlBG3, a GH3 β-glucosidase from Bifidobacterium longum, from human stool. We found that BlBG3 catalyzes the hydrolysis of glycoside furostanol and ginsenoside Rb1 at higher efficiency than other microbial β-glucosidases. Structural analysis of BlBG3 in complex with d-glucose revealed its three unique loops, which form a deep pocket and participate in substrate binding. To understand how substrate is bound to the pocket, molecular docking was performed and the binding interactions of protobioside with BlBG3 were revealed. Mutational study suggested that R484 and H642 are critical for enzymatic activity. Our study presents the first structural and functional analysis of a saponin-processing enzyme from human microbiota.

60 APPLIED LIFE SCIENCES↗