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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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All sourcesNASA NTRSDOE OSTI
DOE OSTI2015

In-service inspection of radioactive waste tanks at the Savannah River Site - 15410

Liquid radioactive wastes from the Savannah River Site (SRS) separation process are stored in large underground carbon steel tanks. The high level wastes are processed in several of the tanks and then transferred by piping to other site facilities for further processing before they are stabilized in a vitrified or grout waste form. Based on waste removal and processing schedules, many of the tanks, will be required to be in service for times exceeding the initial intended life. Until the waste is removed from storage, transferred, and processed, the materials and structures of the tanks must maintain a confinement function by providing a barrier to the environment and by maintaining acceptable structural stability during design basis events, which include loadings from both normal service and abnormal (e.g., earthquake) conditions. A structural integrity program is in place to maintain the structural and leak integrity functions of these waste tanks throughout their intended service life. In-service inspection (ISI) is an essential element of a comprehensive structural integrity program for the waste tanks at the Savannah River Site (SRS). The ISI program was developed to determine the degree of degradation the waste tanks have experienced due to service conditions. As a result of the inspections, an assessment can be made of the effectiveness of corrosion controls for the waste chemistry, which precludes accelerated localized and general corrosion of the waste tanks. Ultrasonic inspections (UT) are performed to detect and quantify the degree of general wall thinning, pitting and cracking as a measure of tank degradation. The results from these inspections through 2013, for the 27 Type III/IIIA tanks, indicate no reportable in-service corrosion degradation in the primary tank (i.e., general, pitting, or cracking). The average wall thickness for all tanks remains above the manufactured nominal thickness minus 0.25 millimeter and the largest pit identified is approximately 1.70 millimeter deep (i.e., less than 10% through-wall). Improvements to the inspection program were recently instituted to provide additional confidence in the degradation rates. Thickness measurements from a single vertical strip along the accessible height of the primary tank have been used as a baseline to compare historical measurements. Changes in wall thickness and pit depths along this vertical strip are utilized to estimate the rate of corrosion degradation. An independent review of the ISI program methodology, results, and path forward was held in August 2009. The review recommended statistical sampling of the tanks to improve the confidence of the single strip inspection program. The statistical sampling plan required that SRS increase the amount of area scanned per tank. Therefore, in addition to the baseline vertical strip that is obtained for historical comparisons, four additional randomly selected vertical strips are inspected. To date, a total of 104 independent vertical strips along the height of the primary tank have been completed. A statistical analysis of the data indicates that at this coverage level there is a 99.5% confidence level that one of the worst 5% of all the vertical strips was inspected. That is, there is a relatively high likelihood that the SRS inspection program has covered one of the most corroded areas of any of the Type III/IIIA waste tanks. These data further support the conclusion that there are no significant indications of wall thinning or pitting. Random sampling will continue to increase the confidence that one of the worst 5% has been inspected. In order to obtain the additional vertical strips, and minimize budget and schedule impacts, data collection speed for the UT system was optimized. Prior to 2009, the system collected data at a rate of 32 square centimeters per minute. The scan rate was increased to 129 - 160 square centimeters per minute by increasing the scanner step and pixel sizes in the data acquisition set-up. Laboratory testing was utilized to optimize the scan index/pixel size such that the requirements for wall thinning and pit detection were still maintained. SRS continues to evaluate improvements to ultrasonic equipment. (authors)

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗
DOE OSTI2019

Quantitative Characterization of a Desalination Membrane Model System by X-ray Photoelectron Spectroscopy

Aromatic polyamide films form the active layer in reverse osmosis desalination membranes. Despite widespread use of this technology, it suffers from low rejection rates for certain water contaminants and from membrane fouling. Through a better understanding of the fundamental surface chemical processes during reverse osmosis desalination, advances in membrane and material design are expected. The recent invention of a molecular layer-by-layer (mLbL) preparation technique yields films that are sufficiently smooth to warrant investigation with high-resolution microscopy and spectroscopy methods. In this study, we present high-resolution, quantitative X-ray photoelectron spectroscopy (XPS) data on the surface chemistry of ultrathin polyamide films that can serve as a model system for desalination membranes. We show that a quantitative analysis of the XPS spectra gives information about the functional groups of the film as well as other compounds present due to the synthesis under ambient conditions. Unpolymerized functional groups are identified and aid in understanding the degree of cross-linking. Investigation of polymers with synchrotron-based XPS requires taking beam-induced changes into account. We quantify X-ray beam damage and show that beam damage to the polyamide is limited, allowing long-term investigation of thin polyamide films. Characterizing mLbL-grown films via high-resolution XPS is the basis for a better understanding of the chemical interplay of polyamide surface functional groups with the major components of desalination systems.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2020

Smart Contract-Defined Secondary Control and Co-Simulation for Smart Solar Inverters using Blockchain Technology

This paper proposes a cooperative control approach using blockchain technology for solar inverters in a photovoltaic system. Moreover, a co-simulation method for smart inverters and a blockchain network is studied. The blockchain assisted-smart inverter (BASI) consists of a solar inverter and an internet of things device as a client node of a blockchain network, which can fully utilize emerging blockchain technologies such as distributed ledger, security functions, and smart contract. The control includes a primary-level droop control in a BASI and smart contract-defined secondary-level supervisory control in a secured blockchain network. The concept of the proposed smart contract-defined control approach is validated by simulation studies using the cyber-physical co-simulation testbed built-in MATLAB/Simulink in a PC interfacing with a Hyperledger-Fabric blockchain software implemented in a PC.

14 SOLAR ENERGY↗
DOE OSTI2012

Algal functional annotation tool

Abstract BACKGROUND: Progress in genome sequencing is proceeding at an exponential pace, and several new algal genomes are becoming available every year. One of the challenges facing the community is the association of protein sequences encoded in the genomes with biological function. While most genome assembly projects generate annotations for predicted protein sequences, they are usually limited and integrate functional terms from a limited number of databases. Another challenge is the use of annotations to interpret large lists of 'interesting' genes generated by genome-scale datasets. Previously, these gene lists had to be analyzed across several independent biological databases, often on a gene-by-gene basis. In contrast, several annotation databases, such as DAVID, integrate data from multiple functional databases and reveal underlying biological themes of large gene lists. While several such databases have been constructed for animals, none is currently available for the study of algae. Due to renewed interest in algae as potential sources of biofuels and the emergence of multiple algal genome sequences, a significant need has arisen for such a database to process the growing compendiums of algal genomic data. DESCRIPTION: The Algal Functional Annotation Tool is a web-based comprehensive analysis suite integrating annotation data from several pathway, ontology, and protein family databases. The current version provides annotation for the model alga Chlamydomonas reinhardtii, and in the future will include additional genomes. The site allows users to interpret large gene lists by identifying associated functional terms, and their enrichment. Additionally, expression data for several experimental conditions were compiled and analyzed to provide an expression-based enrichment search. A tool to search for functionally-related genes based on gene expression across these conditions is also provided. Other features include dynamic visualization of genes on KEGG pathway maps and batch gene identifier conversion. CONCLUSIONS: The Algal Functional Annotation Tool aims to provide an integrated data-mining environment for algal genomics by combining data from multiple annotation databases into a centralized tool. This site is designed to expedite the process of functional annotation and the interpretation of gene lists, such as those derived from high-throughput RNA-seq experiments. The tool is publicly available at http://pathways.mcdb.ucla.edu.

Source record↗
DOE OSTI2020

Taming the fixed-node error in diffusion Monte Carlo via range separation

By combining density-functional theory (DFT) and wave function theory via the range separation (RS) of the interelectronic Coulomb operator, we obtain accurate fixed-node diffusion Monte Carlo (FN-DMC) energies with compact multi-determinant trial wave functions. In particular, we combine here short-range exchange-correlation functionals with a flavor of selected configuration interaction known as configuration interaction using a perturbative selection made iteratively (CIPSI), a scheme that we label RS-DFT-CIPSI. One of the take-home messages of the present study is that RS-DFT-CIPSI trial wave functions yield lower fixed-node energies with more compact multi-determinant expansions than CIPSI, especially for small basis sets. Indeed, as the CIPSI component of RS-DFT-CIPSI is relieved from describing the short-range part of the correlation hole around the electron-electron coalescence points, the number of determinants in the trial wave function required to reach a given accuracy is significantly reduced as compared to a conventional CIPSI calculation. Importantly, by performing various numerical experiments, we evidence that the RS-DFT scheme essentially plays the role of a simple Jastrow factor by mimicking short-range correlation effects, hence avoiding the burden of performing a stochastic optimization. Considering the 55 atomization energies of the Gaussian-1 benchmark set of molecules, we show that using a fixed value of mu = 0.5 bohr(-1) provides effective error cancellations as well as compact trial wave functions, making the present method a good candidate for the accurate description of large chemical systems.

Scemama, Anthony↗
DOE OSTI2016

“Thought experiments” as dry-runs for “tough experiments”: novel approaches to the hydration behavior of oxyanions

We explore the deconvolution of correlations for the interpretation of the microstructural behavior of aqueous electrolytes according to the neutron diffraction with isotopic substitution (NDIS) approach toward the experimental determination of ion coordination numbers of systems involving oxyanions, in particular, sulfate anions. We discuss the alluded interplay in the title of this presentation, emphasized the expectations, and highlight the significance of tackling the challenging NDIS experiments. Specifically, we focus on the potential occurrence of N$2+\atop{i}$ ...SO$2-\atop{4}$ pair formation, identify its signature, suggest novel ways either for the direct probe of the contact ion pair (CIP) strength and the subsequent correction of its effects on the measured coordination numbers, or for the determination of anion coordination numbers free of CIP contributions through the implementation of null-cation environments. For that purpose we perform simulations of NiSO 4 aqueous solutions at ambient conditions to generate the distribution functions required in the analysis (a) to identify the individual partial contributions to the total neutron-weighted distribution function, (b) to isolate and assess the contribution of N$2+\atop{i}$ ...SO$2-\atop{4}$ pair formation, (c) to test the accuracy of the neutron diffraction with isotope substitution based coordination calculations and X-ray diffraction based assumptions, and (d) to describe the water coordination around both the sulfur and oxygen sites of the sulfate anion. In conclusion, we finally discuss the strength of this interplay on the basis of the inherent molecular simulation ability to provide all pair correlation functions that fully characterize the system microstructure and allows us to “reconstruct” the eventual NDIS output, i.e., to take an atomistic “peek” (e.g., see Figure 1) at the local environment around the isotopically-labeled species before any experiment is ever attempted, and ultimately, to test the accuracy of the “measured” NDIS-based coordination numbers against the actual values by the “direct” counting.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2021

Fast inversion, preconditioned quantum linear system solvers, fast Green's-function computation, and fast evaluation of matrix functions

Preconditioning is the most widely used and effective way for treating ill-conditioned linear systems in the context of classical iterative linear system solvers. We introduce a quantum primitive called fast inversion, which can be used as a preconditioner for solving quantum linear systems. The key idea of fast inversion is to directly block encode a matrix inverse through a quantum circuit implementing the inversion of eigenvalues via classical arithmetics. We demonstrate the application of preconditioned linear system solvers for computing single-particle Green's functions of quantum many-body systems, which are widely used in quantum physics, chemistry, and materials science. We analyze the complexities in three scenarios: the Hubbard model, the quantum many-body Hamiltonian in the plane-wave-dual basis, and the Schwinger model. We also provide a method for performing Green's function calculation in second quantization within a fixed-particle manifold and note that this approach may be valuable for simulation more broadly. Aside from solving linear systems, fast inversion also allows us to develop fast algorithms for computing matrix functions, such as the efficient preparation of Gibbs states. Furthermore, we introduce two efficient approaches for such a task, based on the contour-integral formulation and the inverse transform, respectively.

97 MATHEMATICS AND COMPUTING↗
DOE OSTI2025

Hybrid Basis and Multi-Center Grid Method for Strong-Field Processes

We present a time-dependent framework that combines a hybrid basis, consisting of Gaussian-type orbitals (GTOs) and finite-element discrete-variable representation (FEDVR) functions, with a multicenter grid to simulate strong-field and attosecond dynamics in atoms and molecules. The method incorporates the construction of the orthonormal hybrid basis, the evaluation of electronic integrals, a unitary time-propagation scheme, and the extraction of optical and photoelectron observables. Its accuracy and robustness are benchmarked on one-electron systems such as atomic hydrogen and the dihydrogen cation (H$^+_2$) through comparisons with essentially-exact reference results for bound-state energies, high-harmonic generation spectra, photoionization cross sections, and photoelectron momentum distributions. This work establishes the groundwork for its integration with quantum-chemistry methods, which is already operational but will be detailed in future work, thereby enabling ab initio simulations of correlated polyatomic systems in intense ultrafast laser fields.

74 ATOMIC AND MOLECULAR PHYSICS↗
DOE OSTI2014

Noble gas encapsulation into carbon nanotubes: Predictions from analytical model and DFT studies

The energetics for the interaction of the noble gas atoms with the carbon nanotubes (CNTs) are investigated using an analytical model and density functional theory calculations. Encapsulation of the noble gas atoms, He, Ne, Ar, Kr, and Xe into CNTs of various chiralities is studied in detail using an analytical model, developed earlier by Hill and co-workers. The constrained motion of the noble gas atoms along the axes of the CNTs as well as the off-axis motion are discussed. Analyses of the forces, interaction energies, acceptance and suction energies for the encapsulation enable us to predict the optimal CNTs that can encapsulate each of the noble gas atoms. We find that CNTs of radii 2.98 − 4.20 Å (chiral indices, (5,4), (6,4), (9,1), (6,6), and (9,3)) can efficiently encapsulate the He, Ne, Ar, Kr, and Xe atoms, respectively. Endohedral adsorption of all the noble gas atoms is preferred over exohedral adsorption on various CNTs. The results obtained using the analytical model are subsequently compared with the calculations performed with the dispersion-including density functional theory at the M06 − 2X level using a triple-zeta basis set and good qualitative agreement is found. The analytical model is however found to be computationally cheap as the equations can be numerically programmed and the results obtained in comparatively very less time.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2014

Ecological Principles and Guidelines for Managing the Use of Land

The many ways that people have used and managed land throughout history has emerged as a primary cause of land-cover change around the world. Thus, land use and land management increasingly represent a fundamental source of change in the global environment. Despite their global importance, however, many decisions about the management and use of land are made with scant attention to ecological impacts. Thus, ecologists' knowledge of the functioning of Earth's ecosystems is needed to broaden the scientific basis of decisions on land use and management. In response to this need, the Ecological Society of America established a committee to examine the ways that land-use decisions are made and the ways that ecologists could help inform those decisions. This paper reports the scientific findings of that committee. Five principles of ecological science have particular implications for land use and can assure that fundamental processes of Earth's ecosystems are sustained. These ecological principles deal with time, species, place, dis- turbance, and the landscape. The recognition that ecological processes occur within a temporal setting and change over time is fundamental to analyzing the effects of land use. In addition, individual species and networks of interacting species have strong and far-reaching effects on ecological processes. Furthermore, each site or region has a unique set of organisms and abiotic conditions influencing and constraining ecological processes. Distur- bances are important and ubiquitous ecological events whose effects may strongly influence population, com- munity, and ecosystem dynamics. Finally, the size, shape, and spatial relationships of habitat patches on the landscape affect the structure and function of ecosystems. The responses of the land to changes in use and management by people depend on expressions of these fundamental principles in nature. These principles dictate several guidelines for land use. The guidelines give practical rules of thumb for incorporating ecological principles into land-use decision making. These guidelines suggest that land managers should: (1) examine impacts of local decisions in a regional context, (2) plan for long-term change and unexpected events, (3) preserve rare landscape elements and associated species, (4) avoid land uses that deplete natural resources, (5) retain large contiguous or connected areas that contain critical habitats, (6) minimize the intro- duction and spread of nonnative species, (7) avoid or compensate for the effects of development on ecological processes, and (8) implement land-use and management practices that are compatible with the natural potential of the area. Decision makers and citizens are encouraged to consider these guidelines and to include ecological per- spectives in choices on how land is used and managed. The guidelines suggest actions required to develop the science needed by land managers.

Ecology↗
DOE OSTI2012

Structural Basis for Iloprost as a Dual Peroxisome Proliferator-activated Receptor [alpha/delta] Agonist

Iloprost is a prostacyclin analog that has been used to treat many vascular conditions. Peroxisome proliferator-activated receptors (PPARs) are ligand-regulated transcription factors with various important biological effects such as metabolic and cardiovascular physiology. Here, we report the crystal structures of the PPAR{alpha} ligand-binding domain and PPAR{delta} ligand-binding domain bound to iloprost, thus providing unambiguous evidence for the direct interaction between iloprost and PPARs and a structural basis for the recognition of PPAR{alpha}/{delta} by this prostacyclin analog. In addition to conserved contacts for all PPAR{alpha} ligands, iloprost also initiates several specific interactions with PPARs using its unique structural groups. Structural and functional studies of receptor-ligand interactions reveal strong functional correlations of the iloprost-PPAR{alpha}/{delta} interactions as well as the molecular basis of PPAR subtype selectivity toward iloprost ligand. As such, the structural mechanism may provide a more rational template for designing novel compounds targeting PPARs with more favorable pharmacologic impact based on existing iloprost drugs.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2018

Control of Beyond Design Basis Accident in Rbmk with Total Blackout with Prolonged Core Dewatering

A scenario is examined for the development of a beyond design basis accident with loss-of-power for internal needs and functional failures/delays in the actuation of mobile means for emergency cooling RBMK in application to the No. 3 unit of the Kursk NPP. It is shown that actions taken by operating personnel to control pressure in the circulation loop, primarily with the aid of the valves of fast reduction setup for dumping steam in the turbine condensers are effective. The sequence of these actions makes it possible to prevent collapse of the channel tubing at high pressure, preserve the integrity of the reactor space, and effectively limit the accidental emission of radionuclides into the environment.

21 SPECIFIC NUCLEAR REACTORS AND ASSOCIATED PLANTS↗
DOE OSTI2017

Natural orbital description of the halo nucleus 6 He

Ab initio calculations of nuclei face the challenge of simultaneously describing the strong short-range internucleon correlations and the long-range properties of weakly bound halo nucleons. Natural orbitals, which diagonalize the one-body density matrix, provide a basis which is better matched to the physical structure of the many-body wave function. Here, we demonstrate that the use of natural orbitals significantly improves convergence for ab initio no-core configuration interaction calculations of the neutron halo nucleus 6 He, relative to the traditional oscillator basis.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗
DOE OSTI2011

Investigation of the deuteron spin structure at short nucleon-nucleon distances in the reaction of polarized-deuteron fragmentation to cumulative pions

Experimental results on the vector (A{sub y}) and tensor (A{sub yy}) analyzing powers in the fragmentation of 5- and 9-GeV/c polarized deuterons to high-momentum pions in the kinematical region corresponding to pion production on a strongly correlated nucleon pair (cumulative meson production) are presented. The angular and momentum dependences of A{sub yy} are not described by calculations performed in the impulse approximation by using standard deuteron wave functions. An explanation for our data should be sought on the basis of models that treat the deuteron at short distances (deuteron-core region) as a multiquark state-for example, a 6q cluster, whose high orbital angular momentum (D wave) leads to the observed strong dependence of the reaction tensor analyzing power A(d-vector, {pi})X on the pion transverse momentum.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗
DOE OSTI2015

Application of vibrational correlation formalism to internal conversion rate: Case study of Cu{sub n} (n = 3, 6, and 9) and H{sub 2}/Cu{sub 3}

This work reports non-radiative internal conversion (IC) rate constants obtained for Cu{sub n} with n = 3, 6, and 9 and H{sub 2} on Cu{sub 3}. The Time-Dependent Density Functional Theory (TDDFT) method was employed with three different functionals in order to investigate the electronic structures and the absorption spectra. The performance of the generalized gradient approximation of Perdew, Burke and Ernzerhof (PBE) and the hybrid B3LYP and PBE0 exchange correlation functionals in combination with the SVP and the def2-TZVP basis sets was examined. TDDFT results were used as input data to compute internal conversion rate constants. For this purpose, we have developed a program package. A description of the theoretical background used in our numerical implementation and the program input file is presented. In view of future applications of this program package in photoinduced catalysis, we present the analysis of the IC rate processes for the photodissociation of H{sub 2} on Cu{sub 3}. These results showed the applicability of the method and the computational program to identify the vibrational modes in transition metal clusters giving rise to the largest IC rate constant due to their interactions with the excited electronic states occurring in the hot-electron induced dissociation phenomena.

74 ATOMIC AND MOLECULAR PHYSICS↗
DOE OSTI2014

Structural Basis for Resistance to Diverse Classes of NAMPT Inhibitors

Inhibiting NAD biosynthesis by blocking the function of nicotinamide phosphoribosyl transferase (NAMPT) is an attractive therapeutic strategy for targeting tumor metabolism. However, the development of drug resistance commonly limits the efficacy of cancer therapeutics. This study identifies mutations in NAMPT that confer resistance to a novel NAMPT inhibitor, GNE-618, in cell culture and in vivo, thus demonstrating that the cytotoxicity of GNE-618 is on target. We determine the crystal structures of six NAMPT mutants in the apo form and in complex with various inhibitors and use cellular, biochemical and structural data to elucidate two resistance mechanisms. One is the surprising finding of allosteric modulation by mutation of residue Ser165, resulting in unwinding of an α-helix that binds the NAMPT substrate 5-phosphoribosyl-1-pyrophosphate (PRPP). The other mechanism is orthosteric blocking of inhibitor binding by mutations of Gly217. Furthermore, by evaluating a panel of diverse small molecule inhibitors, we unravel inhibitor structure activity relationships on the mutant enzymes. These results provide valuable insights into the design of next generation NAMPT inhibitors that offer improved therapeutic potential by evading certain mechanisms of resistance.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2014

Assessing electronic structure approaches for gas-ligand interactions in metal-organic frameworks: The CO{sub 2}-benzene complex

Adsorption of gas molecules in metal-organic frameworks is governed by many factors, the most dominant of which are the interaction of the gas with open metal sites, and the interaction of the gas with the ligands. Herein, we examine the latter class of interaction in the context of CO{sub 2} binding to benzene. We begin by clarifying the geometry of the CO{sub 2}–benzene complex. We then generate a benchmark binding curve using a coupled-cluster approach with single, double, and perturbative triple excitations [CCSD(T)] at the complete basis set (CBS) limit. Against this ΔCCSD(T)/CBS standard, we evaluate a plethora of electronic structure approximations: Hartree-Fock, second-order Møller-Plesset perturbation theory (MP2) with the resolution-of-the-identity approximation, attenuated MP2, and a number of density functionals with and without different empirical and nonempirical van der Waals corrections. We find that finite-basis MP2 significantly overbinds the complex. On the other hand, even the simplest empirical correction to standard density functionals is sufficient to bring the binding energies to well within 1 kJ/mol of the benchmark, corresponding to an error of less than 10%; PBE-D in particular performs well. Methods that explicitly include nonlocal correlation kernels, such as VV10, vdW-DF2, and ωB97X-V, perform with similar accuracy for this system, as do ωB97X and M06-L.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2016

Solution NMR structure and inhibitory effect against amyloid-β fibrillation of Humanin containing a D-isomerized serine residue

Humanin comprising 24 amino acid residues is a bioactive peptide that has been isolated from the brain tissue of patients with Alzheimer's disease. Humanin reportedly suppressed aging-related death of various cells due to amyloid fibrils and oxidative stress. There are reports that the cytoprotective activity of Humanin was remarkably enhanced by optical isomerization of the Ser14 residue from L to D form, but details of the molecular mechanism remained unclear. Here we demonstrated that Humanin D-Ser14 exhibited potent inhibitory activity against fibrillation of amyloid-β and remarkably higher binding affinity for amyloid-β than that of the Humanin wild-type and S14G mutant. In addition, we determined the solution structure of Humanin D-Ser14 by nuclear magnetic resonance (NMR) and showed that D-isomerization of the Ser14 residue enables drastic conformational rearrangement of Humanin. Furthermore, we identified an amyloid-β-binding site on Humanin D-Ser14 at atomic resolution by NMR. These biophysical and high-resolution structural analyses clearly revealed structure–function relationships of Humanin and explained the driving force of the drastic conformational change and molecular basis of the potent anti-amyloid-β fibrillation activity of Humanin caused by D-isomerization of the Ser14 residue. This is the first study to show correlations between the functional activity, tertiary structure, and partner recognition mode of Humanin and may lead to elucidation of the molecular mechanisms of the cytoprotective activity of Humanin. - Highlights: • Humanin D-Ser14 showed the strongest inhibitory activity against Aβ40 fibrillation. • NMR structure of Humanin D-Ser14 was determined in alcohol/water mixture solution. • Humanin D-Ser14 directly bound Aβ40 stronger than Humanin wild-type and Humanin S14G. • Aβ40 and zinc ion binding sites of Humanin D-Ser14 were identified. • Structure around Ser14 of Humanin is critical for Aβ40 binding and inhibitory activity.

60 APPLIED LIFE SCIENCES↗