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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 NTRS2018

Planned Improvements to the Venus Global Reference Atmospheric Model

The Venus Global Reference Atmospheric Model (Venus-GRAM) is an engineering-level atmospheric model applicable for engineering design analyses, mission planning, and operational decision making. Missions to Venus have generated a wealth of atmospheric data, however, Venus-GRAM has not been updated since its development and release in 2005. GRAM upgrades and maintenance have depended on inconsistent and waning project-specific support. The NASA Science Mission Directorate (SMD) has agreed to provide funding support in Fiscal Year 2018 and 2019 to upgrade the GRAMs. This presentation will provide an overview of Venus-GRAM and the objectives, tasks, and milestones related to the GRAM upgrades.

Justh, H. L.↗
NASA NTRSDate not supplied

The Effects of Chronic Sleep Restriction on Calorie and Macronutrient Intake

Introduction: Chronic sleep restriction (CSR) has been associated with increased calorie intake and increased consumption of fats and carbohydrates, with inconsistent changes in protein. However, the majority of studies have either been observational field studies with no sleep intervention, or laboratory-based studies where food availability may not have reflected participants’ real-world choices. We hypothesized that calorie, fat, and carbohydrate intake would increase during a week of imposed CSR compared to a week of sleep satiation (SS) among individuals living in their home environment. Methods: Twelve healthy participants (6 females) kept a fixed sleep-wake schedule, with a constant waketime, at home for four weeks (actigraphy confirmed compliance). During weeks one and three, participants maintained 9 hours in bed. During weeks two and four, participants were randomly assigned to experimental weeks of 5 and 9 hours of time-in-bed in a crossover design. Participants documented their food consumption during both experimental weeks using a picture-based meal logging application (MealLogger). Intake of calories and macronutrients were classified by two blinded evaluators. Descriptive statistics were calculated in SAS (Cary, NC). Results: Participants averaged 4.43 ± 0.33 (SD) hours of sleep per night during CSR compared to 7.42 ± 0.42 hours during SS. Participants consumed a daily average of 1812 ± 672 kilocalories, 71 ± 31 grams of total fat, 217 ± 69 grams of carbohydrates, and 84 ± 40 grams of protein during CSR, compared to 1682 ± 514 kilocalories, 68 ± 23 grams of total fat, 198 ± 61 grams of carbohydrates, and 77 ± 32 grams of protein during SS. Conclusion: Preliminary descriptive findings suggest that, on average, participants consumed more calories, from an increase in consumption of each macronutrient group, during a week of sleep restriction compared to a week of sleep satiation. Further analysis is needed to determine whether these differences are statistically different and to identify when calories were consumed in each of the experimental conditions.

chronic sleep restriction↗
NASA NTRS1997

Characterization of viable bacteria from Siberian permafrost by 16S rDNA sequencing

Viable bacteria were found in permafrost core samples from the Kolyma-Indigirka lowland of northeast Siberia. The samples were obtained at different depths; the deepest was about 3 million years old. The average temperature of the permafrost is -10 degrees C. Twenty-nine bacterial isolates were characterized by 16S rDNA sequencing and phylogenetic analysis, cell morphology, Gram staining, endospore formation, and growth at 30 degrees C. The majority of the bacterial isolates were rod shaped and grew well at 30 degrees C; but two of them did not grow at or above 28 degrees C, and had optimum growth temperatures around 20 degrees C. Thirty percent of the isolates could form endospores. Phylogenetic analysis revealed that the isolates fell into four categories: high-GC Gram-positive bacteria, beta-proteobacteria, gamma-proteobacteria, and low-GC Gram-positive bacteria. Most high-GC Gram-positive bacteria and beta-proteobacteria, and all gamma-proteobacteria, came from samples with an estimated age of 1.8-3.0 million years (Olyor suite). Most low-GC Gram-positive bacteria came from samples with an estimated age of 5,000-8,000 years (Alas suite).

Non-NASA Center↗
DOE OSTI2023

Development of LpxH Inhibitors Chelating the Active Site Dimanganese Metal Cluster of LpxH

Abstract Despite the widespread emergence of multidrug‐resistant nosocomial Gram‐negative bacterial infections and the major public health threat it brings, no new class of antibiotics for Gram‐negative pathogens has been approved over the past five decades. Therefore, there is an urgent medical need for developing effective novel antibiotics against multidrug‐resistant Gram‐negative pathogens by targeting previously unexploited pathways in these bacteria. To fulfill this crucial need, we have been investigating a series of sulfonyl piperazine compounds targeting LpxH, a dimanganese‐containing UDP‐2,3‐diacylglucosamine hydrolase in the lipid A biosynthetic pathway, as novel antibiotics against clinically important Gram‐negative pathogens. Inspired by a detailed structural analysis of our previous LpxH inhibitors in complex with K. pneumoniae LpxH ( Kp LpxH), here we report the development and structural validation of the first‐in‐class sulfonyl piperazine LpxH inhibitors, JH‐LPH‐45 ( 8 ) and JH‐LPH‐50 ( 13 ), that achieve chelation of the active site dimanganese cluster of Kp LpxH. The chelation of the dimanganese cluster significantly improves the potency of JH‐LPH‐45 ( 8 ) and JH‐LPH‐50 ( 13 ). We expect that further optimization of these proof‐of‐concept dimanganese‐chelating LpxH inhibitors will ultimately lead to the development of more potent LpxH inhibitors for targeting multidrug‐resistant Gram‐negative pathogens.

Pharmacology & Pharmacy↗
DOE OSTI2025

Streptococcus pneumoniae HtrA is a dynamic and monomeric virulence factor capable of forming larger oligomeric complexes

Abstract High‐temperature requirement A (HtrA) proteases are a conserved family of serine proteases central to protein quality control and bacterial virulence. While Gram‐negative and human HtrAs are structurally well studied, Gram‐positive homologs remain essentially uncharacterized. Here, we present the first integrated structural and mechanistic analysis of a Gram‐positive HtrA, from Streptococcus pneumoniae , a virulence factor essential for adhesion and infection in vivo. Proteomic profiling of an htrA knockout and cleavage assays demonstrate that S. pneumoniae HtrA is required for protein quality control, with the PDZ domain mediating substrate recognition. Biochemically, S. pneumoniae HtrA exists exclusively as a monomer in solution, a striking divergence from canonical trimeric HtrAs that we show is shared with other Gram‐positive homologs. NMR analyses reveal that the monomer dynamically samples open and closed conformations, while cryo‐EM of a catalytic mutant identifies a hexamer stabilized by a unique LoopA–PDZ interaction. Together, these findings define S. pneumoniae HtrA as a dynamic monomer with interdomain coupling between its protease and PDZ domains, establishing Gram‐positive HtrAs as a mechanistically divergent subgroup within the HtrA family.

Lee, Eunjeong [Department of Biochemistry and Mole↗
DOE OSTI2021

Reinforced Ammo Can Validation Test Report for Lawrence Livermore National Laboratory

A research effort was conducted to investigate the effects of an unintentional internal detonation of energetic materials on a small transportation container called the “Reinforced Ammo Can” (RAC), which is currently approved for the transport of energetic materials up to 2 grams net explosive weight (NEW) onsite at Lawrence Livermore National Laboratory (LLNL). The project used experimental testing of the containers based on simulated results conducted by a Missouri S & T explosives engineering graduate student while on an internship working in explosives safety at LLNL. The proposed experimental testing consisted of 20 central detonation tests in separate Reinforced Ammo Can containers to verify their high explosive (HE) containment capability. RAC containers are required for transporting secondary explosives on site at LLNL Site 200 in quantities between 300 mg and 2 grams of Trinitrotoluene (TNT) equivalent NEW. Currently, the LLNL Environmental Safety and Health (ES&H) Manual states that the RAC containers are permissible for on-site transportation of secondary explosives up to 2 grams NEW by approved HE handlers with the approval of an Explosives Safety Expert (ESE). Simulated results indicated that tensile failure of the closure mechanism on the container is the most likely failure mode, and showed potential occurrence at the 2 gram NEW threshold. Experimental validation tests were conducted indicating failure/rupture of the containers lid with venting of the detonation products at the 2 gram NEW test threshold with an explosive mass safety factor of 1.3. Failure consisted of impact opening the container latch mechanism resulting in potential ejection of the lid depending on the orientation of the charge within the confinement. This analysis solely is an evaluation of the response of the containment if a detonation were to occur, it does NOT consider the probability of such an event.

42 ENGINEERING↗
NASA NTRS1975

Water hyacinths and alligator weeds for removal of lead and mercury from polluted waters

Removal of lead and mercury by water hyacinths (Eichhornia crassipes) (Mart.) Solms and alligator weeds (Alternanthera philoxeroides) (Mart.) Griesb. was investigated. Water hyacinths demonstrated the ability to remove 0.176 mg of lead and 0.150 mg of mercury per gram of dry plant material from distilled water and river water in a 24-hour period. One acre of water hyacinths is potentially capable of removing 105.6 grams of lead and 90.0 grams of mercury per day. Alligator weeds removed 0.101 mg of lead per gram of dry plant material in a 24-hour period. This same plant also demonstrated the ability to remove a minimum of 0.153 mg of mercury per gram of dry plant material in a six hour period.

Wolverton, B. C.↗
NASA NTRS1987

Improvements in the perturbation simulations of the global reference atmospheric model

The Global Reference Atmospheric Model (GRAM) program includes the capability for simulating pseudo-random perturbations in density, temperature, pressure, or wind components along a simulated reentry trajectory or other path through the atmosphere. Some concerns were expressed by GRAM users, however, that the mean-square perturbation gradients may be too large for small values of the vertical separation Delta z. The present GRAM perturbation simulations, based on a one-step autoregressive model, yield a power spectrum versus wavenumber k which is proportional to k sup -2 at high wavenumbers. This feature also produces mean-square perturbation differences which are directly proportional to Delta z, and mean-square perturbation gradients which are inversely proportional to Delta z. Thus, root-mean-square gradients, (Delta f/Delta z) sub rms, increase with decreasing Delta a as Delta z sup -1/2. A simple modification to GRAM is suggested which overcomes this problem, i.e., which produce root-mean-square gradient that remain bound as Delta z approaches zero. Possible applications of more sophisticated simulation approaches, e.g., second order autoregressive models, or fractal model techniques, were also explored briefly but found to yield improvements which appear too small to justify their considerable added complexity for use in the GRAM programs.

Justus, C. G.↗
NASA NTRS2000

Matching Crew Diet and Crop Food Production in BIO-Plex

This paper matches the BIO-Plex crop food production to the crew diet requirements. The expected average calorie requirement for BIO-Plex is 2,975 Calories per crewmember per day, for a randomly selected crew with a typical level of physical activity. The range of 2,550 to 3,400 Calories will cover about two-thirds of all crews. The exact calorie requirement will depend on the gender composition, individual weights, exercise, and work effort of the selected crew. The expected average crewmember calorie requirement can be met by 430 grams of carbohydrate, 100 grams of fat, and 90 grams of protein per crewmember per day, for a total of 620 grams. Some fat can replaced by carbohydrate. Each crewmember requires only 2 grams of vitamins and minerals per day. Only unusually restricted diets may lack essential nutrients. The Advanced Life Support (ALS) consensus is that BIO-Plex should grow wheat, potato, and soybean, and maybe sweet potato or peanut, and maybe lettuce and tomato. The BIO-Plex Biomass Production System food production and the external food supply must be matched to the crew diet requirement for calories and nutritional balance. The crop production and external supply specifications can each be varied as long as their sum matches the required diet specification. We have wide flexibility in choosing the crops and resupply. We can easily grow one-half the crew calories in one BIO-Plex Biomass Production Chamber (BPC) if we grow only the most productive crops (wheat, potato, and sweet potato) and it we achieve nominal crop productivity. If we assume higher productivity we can grow a wider variety of crops. If we grow one-half of the crew calories, externally supplied foods can easily provide the other half of the calories and balance the diet. We can not grow 95 percent of the crew calories in two BPCs at nominal productivity while growing a balanced diet. We produce maximum calories by growing wheat, potato, and peanut.

Jones, Harry↗
NASA NTRS1996

Varying plant density and harvest time to optimize cowpea leaf yield and nutrient content

Plant density and harvest time were manipulated to optimize vegetative (foliar) productivity of cowpea [Vigna unguiculata (L.) Walp.] canopies for future dietary use in controlled ecological life-support systems as vegetables or salad greens. Productivity was measured as total shoot and edible dry weights (DW), edible yield rate [(EYR) grams DW per square meter per day], shoot harvest index [(SHI) grams DW per edible gram DW total shoot], and yield-efficiency rate [(YER) grams DW edible per square meter per day per grams DW nonedible]. Cowpeas were grown in a greenhouse for leaf-only harvest at 14, 28, 42, 56, 84, or 99 plants/m2 and were harvested 20, 30, 40, or 50 days after planting (DAP). Shoot and edible dry weights increased as plant density and time to harvest increased. A maximum of 1189 g shoot DW/m2 and 594 g edible DW/m2 were achieved at an estimated plant density of 85 plants/m2 and harvest 50 DAP. EYR also increased as plant density and time to harvest increased. An EYR of 11 g m-2 day-1 was predicted to occur at 86 plants/m2 and harvest 50 DAP. SHI and YER were not affected by plant density. However, the highest values of SHI (64%) and YER (1.3 g m-2 day-1 g-1) were attained when cowpeas were harvested 20 DAP. The average fat and ash contents [dry-weight basis (dwb)] of harvested leaves remained constant regardless of harvest time. Average protein content increased from 25% DW at 30 DAP to 45% DW at 50 DAP. Carbohydrate content declined from 50% DW at 30 DAP to 45% DW at 50 DAP. Total dietary fiber content (dwb) of the leaves increased from 19% to 26% as time to harvest increased from 20 to 50 days.

NASA Discipline Life Support Systems↗
NASA NTRS2005

Neutron Diffraction Study Oxygen Dissolution Alpha(sub 2)-Ti3Al

Rietveld refinements of neutron powder diffraction data on alpha(sub 2)-Ti3Al have been performed to determine the crystal structure as a function of interstitial oxygen (O) concentration for three alloys with a Ti/Al ratio of approximately equal to 2.34 and O concentrations of 0.25%, 3.99% and 7.71%. The structures of the allows are hexagonal in space group P6(sub 3)/mmc where Ti and Al atoms populate unique sites with excess Al at the Ti site and O atoms occupy octahedral interstitial sites surrounded by six Ti sites. The length of the c-axis was found to increase linearly as the O occupancy of the interstitial sites increased; this lattice lengthening effect was much less pronounced along the alpha axis. Correspondingly, the increases in the lengths of Ti-Al and Ti-Ti bonds with a major component of their direction parallel to the c-axis were roughly an order of magnitude greater than the increases in the lengths of Ti-al and Ti-Ti bonds more closely aligned with the alpha-axis. Densities calculated form the lattice parameters and occupancy factors fall in the range (4.118 plus or minus 0.004) grams per cubic centimeter to (4.194 plus or minus 0.004) grams per cubic centimeter, and exhibit a nearly linear increase with oxygen concentration. Measured densities of (4.113 plus or minus 0.001) grams per cubic centimeter, (4.146 plus or minus 0.009) grams per cubic centimeter, and (4.191 plus or minus 0.002) grams per cubic centimeter for these alloys agree with the results of the refinements.

Jones, Camille Y.↗
NASA NTRS2008

The NASA MSFC Earth Global Reference Atmospheric Model-2007 Version

Reference or standard atmospheric models have long been used for design and mission planning of various aerospace systems. The NASA/Marshall Space Flight Center (MSFC) Global Reference Atmospheric Model (GRAM) was developed in response to the need for a design reference atmosphere that provides complete global geographical variability, and complete altitude coverage (surface to orbital altitudes) as well as complete seasonal and monthly variability of the thermodynamic variables and wind components. A unique feature of GRAM is that, addition to providing the geographical, height, and monthly variation of the mean atmospheric state, it includes the ability to simulate spatial and temporal perturbations in these atmospheric parameters (e.g. fluctuations due to turbulence and other atmospheric perturbation phenomena). A summary comparing GRAM features to characteristics and features of other reference or standard atmospheric models, can be found Guide to Reference and Standard Atmosphere Models. The original GRAM has undergone a series of improvements over the years with recent additions and changes. The software program is called Earth-GRAM2007 to distinguish it from similar programs for other bodies (e.g. Mars, Venus, Neptune, and Titan). However, in order to make this Technical Memorandum (TM) more readable, the software will be referred to simply as GRAM07 or GRAM unless additional clarity is needed. Section 1 provides an overview of the basic features of GRAM07 including the newly added features. Section 2 provides a more detailed description of GRAM07 and how the model output generated. Section 3 presents sample results. Appendices A and B describe the Global Upper Air Climatic Atlas (GUACA) data and the Global Gridded Air Statistics (GGUAS) database. Appendix C provides instructions for compiling and running GRAM07. Appendix D gives a description of the required NAMELIST format input. Appendix E gives sample output. Appendix F provides a list of available parameters to enable the user to generate special output. Appendix G gives an example and guidance on incorporating GRAM07 as a subroutine in other programs such as trajectory codes or orbital propagation routines.

Leslie, F.W.↗
NASA NTRS2012

Laser Diffraction Techniques Replace Sieving for Lunar Soil Particle Size Distribution Data

Sieving was used extensively until 1999 to determine the particle size distribution of lunar samples. This method is time-consuming, and requires more than a gram of material in order to obtain a result in which one may have confidence. This is demonstrated by the difference in geometric mean and median for samples measured by [1], in which a 14-gram sample produced a geometric mean of approx.52 micrometers, whereas two other samples of ~1.5 grams resulted in gave means of approx.63 and approx.69 micrometers. Sample allocations for sieving are typically much smaller than a gram, and many of the sample allocations received by our lab are 0.5 to 0.25 grams in mass. Basu [2] has described how the finest fraction of the soil is easily lost in the sieving process, and this effect is compounded when sample sizes are small.

Cooper, Bonnie L.↗
DOE OSTI2024

Design and Evaluation of Pyridinyl Sulfonyl Piperazine LpxH Inhibitors with Potent Antibiotic Activity Against Enterobacterales

Enterobacterales, a large order of Gram-negative bacteria, including Escherichia coli and Klebsiella pneumoniae, are major causes of urinary tract and gastrointestinal infections, pneumonia, and other diseases in healthcare settings and communities. ESBL-producing Enterobacterales and carbapenem-resistant Enterobacterales can break down commonly used antibiotics, with some strains being resistant to all available antibiotics. This public health threat necessitates the development of novel antibiotics, ideally targeting new pathways in these bacteria. Gram-negative bacteria possess an outer membrane enriched with lipid A, a saccharolipid that serves as the membrane anchor of lipopolysaccharides and the active component of the bacterial endotoxin, causing septic shock. The biosynthesis of lipid A is crucial for the viability of Gram-negative bacteria, and as an essential enzyme in this process, LpxH has emerged as a promising target for developing novel antibiotics against multidrugresistant Gram-negative pathogens. Here, we report the development of pyridinyl sulfonyl piperazine LpxH inhibitors. Among them, ortho-substituted pyridinyl compounds significantly boost LpxH inhibition and antibiotic activity over the original phenyl series. Structural and QM/MM analyses reveal that these improved activities are primarily due to the enhanced interaction between F141 of the LpxH insertion lid and the pyridinyl group. Incorporation of the N-methyl-N-phenyl-methanesulfonamide moiety into the pyridinyl sulfonyl piperazine backbone results in JHLPH- 106 and JH-LPH-107, both of which exhibit potent antibiotic activity against wild-type Enterobacterales such as K. pneumoniae and E. coli. JH-LPH-107 exhibits a low rate of spontaneous resistance and a high safety window in vitro, rendering it an excellent lead for further clinical development.

60 APPLIED LIFE SCIENCES↗
NASA NTRS1986

Predatory prokaryotes: predation and primary consumption evolved in bacteria

Two kinds of predatory bacteria have been observed and characterized by light and electron microscopy in samples from freshwater sulfurous lakes in northeastern Spain. The first bacterium, named Vampirococcus, is Gram-negative and ovoidal (0.6 micrometer wide). An anaerobic epibiont, it adheres to the surface of phototrophic bacteria (Chromatium spp.) by specific attachment structures and, as it grows and divides by fission, destroys its prey. An important in situ predatory role can be inferred for Vampirococcus from direct counts in natural samples. The second bacterium, named Daptobacter, is a Gram-negative, facultatively anaerobic straight rod (0.5 x 1.5 micrometers) with a single polar flagellum, which collides, penetrates, and grows inside the cytoplasm of its prey (several genera of Chromatiaceae). Considering also the well-known case of Bdellovibrio, a Gram-negative, aerobic curved rod that penetrates and divides in the periplasmic space of many chemotrophic Gram-negative bacteria, there are three types of predatory prokaryotes presently known (epibiotic, cytoplasmic, and periplasmic). Thus, we conclude that antagonistic relationships such as primary consumption, predation, and scavenging had already evolved in microbial ecosystems prior to the appearance of eukaryotes. Furthermore, because they represent methods by which prokaryotes can penetrate other prokaryotes in the absence of phagocytosis, these associations can be considered preadaptation for the origin of intracellular organelles.

Non-NASA Center↗
NASA NTRS1993

Assignment of fatty acid-beta-oxidizing syntrophic bacteria to Syntrophomonadaceae fam. nov. on the basis of 16S rRNA sequence analyses

After enrichment from Chinese rural anaerobic digestor sludge, anaerobic, sporing and nonsporing, saturated fatty acid-beta-oxidizing syntrophic bacteria were isolated as cocultures with H2- and formate-utilizing Methanospirillum hungatei or Desulfovibrio sp. strain G-11. The syntrophs degraded C4 to C8 saturated fatty acids, including isobutyrate and 2-methylbutyrate. They were adapted to grow on crotonate and were isolated as pure cultures. The crotonate-grown pure cultures alone did not grow on butyrate in either the presence or the absence of some common electron acceptors. However, when they were reconstituted with M. hungatei, growth on butyrate again occurred. In contrast, crotonate-grown Clostridium kluyveri and Clostridium sticklandii, as well as Clostridium sporogenes, failed to grow on butyrate when these organisms were cocultured with M. hungatei. The crotonate-grown pure subcultures of the syntrophs described above were subjected to 16S rRNA sequence analysis. Several previously documented fatty acid-beta-oxidizing syntrophs grown in pure cultures with crotonate were also subjected to comparative sequence analyses. The sequence analyses revealed that the new sporing and nonsporing isolates and other syntrophs that we sequenced, which had either gram-negative or gram-positive cell wall ultrastructure, all belonged to the phylogenetically gram-positive phylum. They were not closely related to any of the previously known subdivisions in the gram-positive phylum with which they were compared, but were closely related to each other, forming a new subdivision in the phylum. We recommend that this group be designated Syntrophomonadaceae fam. nov.; a description is given.

NASA Discipline Number 52-30↗
DOE OSTI2024

Self-Assembling and Pore-Forming Peptoids as Antimicrobial Biomaterials

Bacterial infections have been a serious threat to mankind throughout history. Natural antimicrobial peptides (AMPs) and their membrane-disruption mechanism have generated an immense interest in the design and development of synthetic mimetics that could overcome the intrinsic drawbacks of AMPs, such as their susceptibility to proteolytic degradation. Herein, by exploiting the self-assembly and pore-forming capabilities of sequence-defined peptoids, we discovered a new family of low molecular weight peptoid antibiotics that exhibit excellent broad-spectrum activity and high selectivity toward a panel of clinically significant Gram-positive and Gram-negative bacterial strains, including vancomycin-resistant E. faecalis (VREF), methicillin-resistant S. aureus (MRSA), methicillin-resistant S. epidermidis (MRSE), E. coli, P. aeruginosa, and K. pneumoniae. Tuning peptoid sidechain chemistry and structure enabled us to tune the efficacy of antimicrobial activity. Mechanistic studies using Transmission Electron Microscopy (TEM), bacterial membrane depolarization and lysis, and time-kill kinetics assays along with molecular dynamics simulations reveal that these peptoids kill both Gram-positive and Gram-negative bacteria through a membrane-disruption mechanism. In conclusion, these robust and biocompatible peptoid-based antibiotics can provide a valuable tool for combating the emerging drug resistance.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Molecular dynamics simulations of the secondary-binding site in disaccharide-modified glycopeptide antibiotics

Oritavancin is a semisynthetic glycopeptide antibiotic used to treat severe infections by multidrug-resistant Gram-positive pathogens. Oritavancin is known to be a thousand times more potent than vancomycin against Gram-positive bacteria due to the additional interactions with bacterial peptidoglycan (PG) facilitated by a secondary-binding site. The presence of this secondary-binding site is evident in desleucyl-oritavancin, an Edman degradation product of oritavancin, still retaining its potency against Gram-positive bacteria, whereas desleucyl-vancomycin is devoid of any antimicrobial activities. Herein, using explicit solvent molecular dynamics (MD) simulations, steered MD simulations, and umbrella sampling, we show evidence of a secondary-binding site mediated by the disaccharide-modified hydrophobic sidechain of oritavancin interactions with the pentaglycyl-bridge segment of the PG. The interactions were characterized through comparison to the interaction of PG with chloroeremomycin, vancomycin, and the desleucyl analogs of the glycopeptides. Our results show that the enhanced binding of oritavancin to PG over the binding of the other complexes studied is due to an increase in the hydrophobic effect, electrostatic and van der Waals interactions, and not the average number of hydrogen bonds. Our ranking of the binding interactions of the biomolecular complexes directly correlates with the order based on their experimental minimum inhibitory concentrations. The results of our simulations provide insight into the modification of glycopeptides to increase their antimicrobial activities or the design of novel antibiotics against pathogenic Gram-positive bacteria.

60 APPLIED LIFE SCIENCES↗