Search NASA⌕ Search

SEARCH · Search NASA

Results for “Conformal prediction”

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.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 271 records · Page 15
All sourcesNASA NTRSDOE OSTI
DOE OSTI2023

Decoupling of catalysis and transition state analog binding from mutations throughout a phosphatase revealed by high-throughput enzymology

Using high-throughput microfluidic enzyme kinetics (HT-MEK), we measured over 9,000 inhibition curves detailing impacts of 1,004 single-site mutations throughout the alkaline phosphatase PafA on binding affinity for two transition state analogs (TSAs), vanadate and tungstate. As predicted by catalytic models invoking transition state complementary, mutations to active site and active-site-contacting residues had highly similar impacts on catalysis and TSA binding. Unexpectedly, most mutations to more distal residues that reduced catalysis had little or no impact on TSA binding and many even increased tungstate affinity. These disparate effects can be accounted for by a model in which distal mutations alter the enzyme’s conformational landscape, increasing the occupancy of microstates that are catalytically less effective but better able to accommodate larger transition state analogs. In support of this ensemble model, glycine substitutions (rather than valine) were more likely to increase tungstate affinity (but not more likely to impact catalysis), presumably due to increased conformational flexibility that allows previously disfavored microstates to increase in occupancy. These results indicate that residues throughout an enzyme provide specificity for the transition state and discriminate against analogs that are larger only by tenths of an Ångström. Thus, engineering enzymes that rival the most powerful natural enzymes will likely require consideration of distal residues that shape the enzyme’s conformational landscape and fine-tune active-site residues. Biologically, the evolution of extensive communication between the active site and remote residues to aid catalysis may have provided the foundation for allostery to make it a highly evolvable trait.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Scalable Thin Light-Emitting Diode (LED) Light Sheet Platform

The goal of the Scalable Thin Light-Emitting Diode (LED) Light Sheet Platform project is to derisk the manufacturing scalability for a high chip count heterogeneous smart lighting platform, with the potential to enable significant energy savings through dynamic directional light control and custom. Specifically, the project derisks the scalability of a disruptive new computer controlled microassembly fabrication process SRI International is developing, to address fundamental cost barriers to mass production of high chip count systems. This is key for enabling mass adoption and thus maximum societal energy savings impact. The LED light sheet technology is a smart illumination platform that can be applied to lighting, signage, and display. It has features and a form factor similar to bendable or conformal OLED light sheets but uses more efficient LEDs with a remote phosphor layer that is very close to the LED to deliver a luminous efficacy that exceeds 125 lumen/Watt and enable > 50% Lighting Application Efficiency (LAE) energy savings. During Budget Period 1 (BP1), all of the BP1 milestones were successfully completed: (M2.0.1) Design demonstrator details that will meet the final project goals, (M6.1.1) Show lighting output model can predict illuminance, spatial, spectral distribution for specific light-sheet designs and use case, (M3.2.1) Automated loading supports 200 chip arrays, and (M3.3.1) Finish first interconnect process run for 200 chip array. The BP1 Go/No-Go Decision Point (G/NG 1) 200 chip demonstrator sample was in the process of final assembly and test at the end of BP1 on December 31, 2023. The objective was successfully achieved on January 16, 2024, when a wired 200-chip sample underwent confirmation testing that demonstrated a 93.75% first pass electrical yield that successfully exceeded the 75% first-pass electrical yield BP1 G/NG requirement. In addition, all 93.75% of the sample devices lit up, further demonstrating the ability to assemble and transfer small LED chips without damaging their functionality.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗
DOE OSTI2025

2025 ASMS Investigation of the Collision-Induced Dissociation Mechanism of Protonated TODGA with IRIS

Title (20 words): Investigation of the Collision-Induced Dissociation Mechanism of Protonated TODGA with IRIS Introduction (120 words): One of the challenges facing wide-spread adoption of nuclear power is the development of efficient separation processes for used nuclear fuel. The molecules in separation processes are subjected to an extreme environment due to the high radiation fields from the used fuel and highly acidic media used for fuel dissolution, which results in significant molecular degradation, leading to reduced process efficiency. These degradation products must be identified and studied so mitigation strategies can be developed to maintain process efficiency. However, complex systems can have many degradation products, complicating identification. Untargeted analysis tools could be used to understand radiation chemistry in complex systems. However, this would necessitate improved understanding of the gas-phase fragmentation mechanisms of fuel cycle molecules like tetraoctyldiglycolamide (TODGA). Methods (120 words): The gas-phase fragmentation of protonated TODGA was investigated using collision-induced dissociation (CID), resonance ejection, and infrared ion spectroscopy (IRIS). CID and resonance ejection experiments were conducted using a Bruker Daltonics (Bremen, Gemany) SolariX XR fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer. IRIS spectra of protonated TODGA and its two CID fragmentation products were measured using a modified Bruker amaZon Speed ETD 3D quadrupole ion trap mass spectrometer coupled to the Free Electron Lasers for Infrared eXperiments (FELIX) free electron laser. Measured spectra were compared with density functional theory (DFT) calculations using the Gaussian 16, Revision C.02 software package with the ?B97X-D functional and def2-TZVPP basis sets. Candidate structures were generated using the CREST 3.0 conformational sampling software tool. Preliminary Data (300 words): Collision-induced dissociation of protonated TODGA ([C36H73N2O3]+, m/z=581.562) results two fragment ions, one at m/z=340.285 assigned as [C20H38NO3]+ and the other at m/z=312.290, assigned as [C19H38NO2]+. Based on the assigned formula and the structure of protonated TODGA, the fragment at m/z=340.285 is likely formed from elimination of neutral dioctylamine. Comparison of the IRIS spectrum of m/z=340.285 with DFT predictions suggests it contains a ring structure, and is assigned as N-octyl-N-(6-oxo-1,4-dioxan-2-ylidene)octan-1-aminium. Based on this structure and the structure of protonated TODGA, we hypothesize this fragment formed from elimination of neutral dioctylamine followed by a ring closure mechanism. Comparison of the IRIS spectrum of the fragment at m/z=312.290 with DFT predictions also indicated the presence of a ring structure, assigned as N-(1,3-dioxolan-4-ylidene)-N-octyloctan-1-aminium. This product could be formed from elimination of carbon monoxide from the ring of m/z=340.285 as a sequential fragmentation or formed directly from protonated TODGA via elimination of neutral N,N-dioctylformamide followed by a ring closure. Resonance ejection experiments where m/z=340 was continuously ejected from the IRC cell showed no decrease in intensity of m/z=312.290 across several collision energies, suggesting that the later, direct formation mechanism, dominates. The location of the ionizing proton in protonated TODGA is important for modeling the fragmentation mechanisms. DFT calculations suggested that the position of bands involving the coupled vibrations of the amide C—N and C=O bonds in TODGA are the most sensitive to proton location. Evaluation of the IRIS spectrum of protonated TODGA suggests that the ionizing proton is located between the two amid oxygens. This protonation location was calculated to lie approximately 30 kJ/mol lower in energy than the next lowest energy location, with the proton located solely on one of the amide oxygens. Novel aspect (20 words): Infrared ion spectroscopy combined with resonance ejection experiments and density functional theory to probe the collision-induced dissociation mechanism of tetraoctyldiglycolamide.

37 - INORGANIC, ORGANIC, PHYSICAL AND ANALYTICAL C↗
DOE OSTI2020

Polymer principles behind solubilizing lignin with organic cosolvents for bioenergy

Lignin solubilization is key to a viable biorefinery because its removal leads to facile deconstruction of biomass and because the isolated lignin can serve to derive precursors of novel high-value materials. The mixing of organic solvents with water has been shown to improve biomass fractionation and lignin conversion reactions. However, generally-applicable solubilization strategies are lacking because of the remarkable variability of lignin across plant feedstocks. Here, to obtain a predictive understanding of lignin solvation, we perform molecular dynamics simulations of model lignin polymers in two mixtures of water with polar aprotic solvents: tetrahydrofuran (THF) : water and γ-valerolactone (GVL) : water. The model lignins include H-, G- and S-only homopolymers and lignins with an S : G 1 : 1 ratio. We find that a well-established theory of self-avoiding polymers in a “good” solvent describes accurately the physical conformations of all types of lignin in both solvents. As the degree of methoxy substitution increases in the homopolymers, the distributions of the lignin radius of gyration and the Flory exponent ν , which describes the lignin-solvent interactions, do not change in THF : water, while ν shifts to slightly higher values in GVL : water. We attribute this increase to the interaction between the methyl group of GVL with the lignin methoxy groups. We also find that the reduction in the lignin radius of gyration due to branching is accurately described by the Zimm–Stockmayer theory for both THF : water and GVL : water. The above findings validate the applicability of polymer physics concepts to lignin and suggest that GVL : water may have the most favorable interaction with S-lignin, whereas the interactions of THF : water with lignin are independent of lignin monomeric content.

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

Uncovering Non-Fermi-Liquid Behavior in Hund Metals: Conformal Field Theory Analysis of an SU(2)×SU(3) Spin-Orbital Kondo Model

Hund metals have attracted attention in recent years due to their unconventional superconductivity, which supposedly originates from non-Fermi-liquid (NFL) properties of the normal state. When studying Hund metals using dynamical mean-field theory, one arrives at a self-consistent “Hund impurity problem” involving a multiorbital quantum impurity with nonzero Hund coupling interacting with a metallic bath. If its spin and orbital degrees of freedom are screened at different energy scales, T sp < T orb , the intermediate energy window is governed by a novel NFL fixed point, whose nature had not yet been clarified. We resolve this problem by providing an analytical solution of a paradigmatic example of a Hund impurity problem, involving two spin and three orbital degrees of freedom. To this end, we combine a state-of-the-art implementation of the numerical renormalization group, capable of exploiting non-Abelian symmetries, with a generalization of Affleck and Ludwig’s conformal field theory (CFT) approach for multichannel Kondo models. We characterize the NFL fixed point of Hund metals in detail for a Kondo model with an impurity forming an SU ( 2 ) × SU ( 3 ) spin-orbital multiplet, tuned such that the NFL energy window is very wide. The impurity’s spin and orbital susceptibilities then exhibit striking power-law behavior, which we explain using CFT arguments. We find excellent agreement between CFT predictions and numerical renormalization group results. Our main physical conclusion is that the regime of spin-orbital separation, where orbital degrees of freedom have been screened but spin degrees of freedom have not, features anomalously strong local spin fluctuations: the impurity susceptibility increases as χ sp imp ~ ω – γ , with γ > 1 .

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗
DOE OSTI2022

Normalization of ZZ instanton amplitudes in minimal string theory

We use insights from string field theory to analyze and cure the divergences in the cylinder diagram in minimal string theory with both boundaries lying on a ZZ brane. We focus on theories with worldsheet matter consisting of the (2, p) minimal model plus Liouville theory, with total central charge 26, together with the usual bc-ghosts. The string field theory procedure gives a finite, purely imaginary normalization constant for non-perturbative effects in minimal string theory, or doubly non-perturbative effects in JT gravity. We find precise agreement with the prediction from the dual double-scaled one-matrix integral. We also make a few remarks about the extension of this result to the more general (p', p) minimal string.

2D gravity↗
DOE OSTI2022

Power-law inflation satisfies Penrose’s Weyl curvature hypothesis

Based on entropy considerations and the arrow of time Penrose argued that the Universe must have started in a special initial singularity with vanishing Weyl curvature. This is often interpreted to be at odds with inflation. Here we argue just the opposite, that Penrose’s persuasions are in fact consistent with inflation. Using the example of power law inflation, we show that inflation begins with a past null singularity, where Weyl tensor vanishes when the metric is initially exactly conformally flat. This initial state precisely obeys Penrose’s conditions. The initial null singularity breaks T-reversal spontaneously and picks the arrow of time. It can be regulated and interpreted as a creation of a universe from nothing, initially fitting in a bubble of Planckian size when it materializes. Penrose’s initial conditions are favored by the initial O(4) symmetry of the bubble, selected by extremality of the regulated Euclidean action. The predicted observables are marginally in tension with the data, but they can fit if small corrections to power law inflation kick in during the last 60⁢e-folds.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2025

Statistical evaluation of microscale stress conditions leading to void nucleation in the weak shock regime

Here, we investigate the heterogeneity of the stress state driven by anisotropic deformation response at the single crystal level through five statistical volume element (SVE) calculations of polycrystalline BCC tantalum. This work focuses on grain boundaries as a prominent material defect type prone to void nucleation based upon experimental observations of predominantly intergranular void nucleation in this material. The SVEs are constructed to be statistically representative of larger volumes of material and are meshed such that mean and standard deviation of grain size and orientation information is reconstructed. The computational meshes feature hexahedral (brick) elements and smooth conformal grain boundaries where significant stress concentration is known to occur, a tail effect of interest in the extreme events process of dynamic ductile damage. An existing micromechanical crystallographic plasticity model shown to capture the single crystal behavior of BCC tantalum well is used to perform the polycrystal calculations. The model includes representation of the non-Schmid effect of non-planar screw dislocation kinetics in tantalum. A three-dimensional stress state time profile predicted by damage modeling of a flyer plate impact experiment is applied as boundary conditions to each SVE. Resulting grain boundary stress state statistics are strongly non-Gaussian. Significant structural evolution is observed within the compressive hold before unloading into tension in the stress profile. Strong angular dependence of grain boundary traction magnitude with shock direction is observed. Non-Schmid effects continue to suggest their influence on propensity of microstructural defect types to nucleate voids. A general void nucleation criterion is proposed using probability theory. The general framework is specified to polycrystalline BCC tantalum in the weak shock regime to include the SVE calculations and literature molecular dynamics calculations of grain boundary void nucleation strength. Probability density functions (PDFs) are used to describe the interaction between the local stress state heterogeneity and the distributed grain boundary void nucleation strength state. A causation entropy maximization procedure removes the requirement for ad hoc selection of a PDF functional form and provides a rigorous procedure for data-based PDF determination. The resulting physically informed PDF describes the spatial appearance frequency of nucleated voids as a function of applied macroscale pressure. Lower length scale physics are thus packaged in a precise and computationally efficient way to provide computational plasticity insight to macroscale dynamic ductile damage models.

36 MATERIALS SCIENCE↗
DOE OSTI2025

Substituent size versus metal binding of inhibitors with variants of influenza endonuclease

The influenza virus causes a significant burden of illness each year. Although vaccination is the most effective method to prevent seasonal influenza infection, viral escape mechanisms make vaccine composition difficult to predict. Antivirals are crucial for decreasing rates of morbidity and mortality from influenza viral infection. The newest anti-influenza drugs target the RNA-dependent RNA polymerase acidic N-terminal (PA N ) endonuclease, a critical component of influenza viral replication machinery. This study examines the structure of inhibitors of PAN that utilize a hydroxypyridinone-based metal-binding pharmacophore (MBP). Specifically, this report explores how the size of substituent groups impacts the binding conformation and affinity of a series of compounds against both wild-type (WT) and resistance mutant strains, I38T and E23K. Co-crystal structures revealed that the distance between compounds and enzyme residue 38 was conserved to maintain strong interactions, resulting in deviations from ideal coordination geometries at the active site metal centers. This suggests the interactions with residue 38 with each compound is important and can impact inhibitor potency as a consequence of distortions in the metal binding geometry of the compounds.

Endonuclease↗
DOE OSTI2022

Computational identification of HCV neutralizing antibodies with a common HCDR3 disulfide bond motif in the antibody repertoires of infected individuals

Despite recent success in hepatitis C virus (HCV) treatment using antivirals, an HCV vaccine is still needed to prevent reinfections in treated patients, to avert the emergence of drug-resistant strains, and to provide protection for people with no access to the antiviral therapeutics. The early production of broadly neutralizing antibodies (bNAbs) associates with HCV clearance. Several potent bNAbs bind a conserved HCV glycoprotein E2 epitope using an unusual heavy chain complementarity determining region 3 (HCDR3) containing an intra-loop disulfide bond. Isolation of additional structurally-homologous bNAbs would facilitate the recognition of key determinants of such bNAbs and guide rational vaccine design. Here we report the identification of new antibodies containing an HCDR3 disulfide bond motif using computational screening with the Rosetta software. Using the newly-discovered and already-known members of this antibody family, we review the required HCDR3 amino acid composition and propose determinants for the bent versus straight HCDR3 loop conformation observed in these antibodies.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Unraveling Electronic Effects that Influence the Bimolecular Chemistry of Fluorinated Criegee Intermediates

Ozonolysis is important for the removal of unsaturated volatile organic compounds emitted into the Earth's atmosphere. The alkene + ozone reaction (alkene ozonolysis) forms a carbonyl oxide – a Criegee intermediate (CI). CIs are interesting from an atmospheric chemistry perspective. They are implicated in enhancing the oxidizing capacity of the troposphere and in secondary organic aerosol formation. CIs may participate in bimolecular reactions with trace atmospheric vapors like water and methanol. Here, the chemistry of the two isomers of CFHOO and of CF 3 CHOO with water, water dimer, and methanol is explored. The present study confirms that the syn-conformer is the minimum energy structure for both CIs and that the reactions of anti-CFHOO display slightly lower activation energies cf. syn-CFHOO, thus promoting faster reaction. For both syn- and anti-CFHOO, the energy barrier in the pathway to adding water, water dimer, or methanol is lower—and the overall reaction exoergicity greater—than for the corresponding reactions involving the nonfluorinated analogue, CH 2 OO. Here, the corresponding bimolecular reaction rates are thus predicted to be faster for CFHOO than CH 2 OO. Similar reactivity trends are found when comparing the same reactions of syn-CF 3 CHOO, cf. syn-CH 3 CHOO, but not when comparing the energetics of the reactions involving anti-CF 3 CHOO cf. anti-CH 3 CHOO.

Guidry, Lily M. [University of Louisiana at Lafaye↗
DOE OSTI2024

Direct numerical simulations of three-component Rayleigh–Taylor mixing and an improved model for multicomponent reacting mixtures

We present direct numerical simulations of a three-layer Rayleigh–Taylor instability (RTI) problem with a configuration based on the experiments of Suchandra & Ranjan ( J. Fluid Mech. , vol. 974, 2023, A35) and Jacobs & Dalziel ( J. Fluid Mech. , vol. 542, 2005, pp. 251–279). The problem consists of a layer of light fluid between two layers of heavy fluid with an Atwood number of 0.3. These simulations are first validated through comparison with available experimental data. The validated simulations are then utilized to analyse statistics in this three-component flow. First, length scales are examined utilizing spectra and two-point spatial correlations of velocity and species concentration fluctuations. Next, joint probability density functions (p.d.f.s) of species concentration are compared against several model p.d.f.s representing generalizations of the bivariate beta distribution. Notably, the joint p.d.f.s do not appear to be accurately described by a Dirichlet distribution, indicating the marginal distributions do not conform to a beta distribution. Finally, similarity of the present configuration to three-component mixing found in inertial confinement fusion (ICF) applications is exploited to develop and validate an improved model for the impact of multicomponent mixing on thermonuclear (TN) reaction rates. A single time instant from the present simulations is chosen for a TN burn calculation under the hypothetical assumption of ICF materials and temperatures. Total TN output from this second calculation is then compared against the prediction of the improved model. The new model is found to accurately predict TN reaction rates in both premixed and non-premixed configurations.

42 ENGINEERING↗
DOE OSTI2022

Using machine-learning to understand complex microstructural effects on the mechanical behavior of Ti-6Al-4V alloys

Structural materials properties are highly dependent on their microstructure. Their microstructure is in turn affected by multiple fabrication and thermo-mechanical treatment parameters, all of which conform a highly-dimensional parametric space with often hidden correlations that are difficult to extract by experimentation alone. This is particularly true for alloys of the dual-phase Ti-6Al-4V family, with their greatly complex and rich microstructures, which combine several intrinsic length scales associated with multiple grain and subgrain structures, grains with different crystal lattices (α and β phases), and complex chemistry. In this paper we use a comprehensive set of machine learning techniques to develop predictive tools relating the yield strength and hardening rate of these alloys to a set of input parameters covering extensive ranges. The data generator is a finite-element crystal plasticity model for polycrystal deformation that takes into account slip anisotropy and employs standard dislocation evolution models for the α and β phases of Ti-based alloys. Our dataset includes over two thousand independent simulations and is used to train the machine learning models, which are then used to establish correlations between microstructural parameters and the alloys’ mechanical response. Our results point to the most influential parameters affecting yield strength and hardening rate, information that can then be used to guide experimental synthesis and characterization efforts to save time and resources.

36 MATERIALS SCIENCE↗
DOE OSTI2023

The C 2 H 4 O isomers in the oxidation of ethylene

A combined rotational spectroscopy, thermochemistry, and kinetic modeling study explores the mechanism of acetaldehyde (ethanal), vinyl alcohol (ethenol), and ethylene oxide (oxirane) formation in the oxidation of ethylene (ethene). Multiplexed quantitative detection of oxidation intermediates and products exiting a SiO 2 / SiC microreactor at 1700 K is demonstrated with the BrightSpec W-band chirped-pulse Fourier transform millimeter-wave spectrometer. The broadband rotational spectrum contains transitions of formaldehyde (CH 2 O), methoxy (CH 3 O), methanol (CH 3 OH), ketene (CH 2 CO), acetaldehyde (CH 3 CHO), syn-vinyl alcohol (syn- CH 2 CHOH), anti-vinyl alcohol (anti-CH 2 CHOH), oxirane (c-CH 2 OCH 2 ), propyne (CH 3 CCH), and syn-propanal (syn-CH 3 CH 2 CHO). We focus on the three C 2 H 4 O species and deduce their concentration ratio [CH 3 CHO]:[CH 2 CHOH]:[c-CH 2 OCH 2 ] = 1:0.7(2):0.06(2) by comparing the observed line intensities to those simulated with the PGOPHER software. Detailed thermochemistry of the C 2 H 4 O isomers and conformers is provided by Active Thermochemical Tables. The observed excess concentrations of vinyl alcohol and oxirane relative to the more stable acetaldehyde compared to the equilibrium ratio at 1700 K (1:0.087:0.000024), point to direct chemical pathways to these higher energy isomers. The mechanism for the formation of the three C 2 H 4 O isomers is analyzed using a 0-D homogenous reactor kinetics simulation for ethylene oxidation. The ratios of the C 2 H 4 O isomers concentrations predicted by the kinetic model are compared to the experimental values.

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

Cryo-EM confirms a common fibril fold in the heart of four patients with ATTRwt amyloidosis

ATTR amyloidosis results from the conversion of transthyretin into amyloid fibrils that deposit in tissues causing organ failure and death. This conversion is facilitated by mutations in ATTRv amyloidosis, or aging in ATTRwt amyloidosis. ATTRv amyloidosis exhibits extreme phenotypic variability, whereas ATTRwt amyloidosis presentation is consistent and predictable. Previously, we found unique structural variabilities in cardiac amyloid fibrils from polyneuropathic ATTRv-I84S patients. In contrast, cardiac fibrils from five genotypically different patients with cardiomyopathy or mixed phenotypes are structurally homogeneous. To understand fibril structure’s impact on phenotype, it is necessary to study the fibrils from multiple patients sharing genotype and phenotype. Here we show the cryo-electron microscopy structures of fibrils extracted from four cardiomyopathic ATTRwt amyloidosis patients. Our study confirms that they share identical conformations with minimal structural variability, consistent with their homogenous clinical presentation. Our study contributes to the understanding of ATTR amyloidosis biopathology and calls for further studies.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Ca X ML: Chemistry‐informed machine learning explains mutual changes between protein conformations and calcium ions in calcium‐binding proteins using structural and topological features

Proteins' flexibility is a feature in communicating changes in cell signaling instigated by binding with secondary messengers, such as calcium ions, associated with the coordination of muscle contraction, neurotransmitter release, and gene expression. When binding with the disordered parts of a protein, calcium ions must balance their charge states with the shape of calcium-binding proteins and their versatile pool of partners depending on the circumstances they transmit. Accurately determining the ionic charges of those ions is essential for understanding their role in such processes. However, it is unclear whether the limited experimental data available can be effectively used to train models to accurately predict the charges of calcium-binding protein variants. Here, we developed a chemistry-informed, machine-learning algorithm that implements a game theoretic approach to explain the output of a machine-learning model without the prerequisite of an excessively large database for high-performance prediction of atomic charges. We used the ab initio electronic structure data representing calcium ions and the structures of the disordered segments of calcium-binding peptides with surrounding water molecules to train several explainable models. Network theory was used to extract the topological features of atomic interactions in the structurally complex data dictated by the coordination chemistry of a calcium ion, a potent indicator of its charge state in protein. Our design created a computational tool of Ca X ML, which provided a framework of explainable machine learning model to annotate ionic charges of calcium ions in calcium-binding proteins in response to the chemical changes in an environment. Our framework will provide new insights into protein design for engineering functionality based on the limited size of scientific data in a genome space.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗