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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 253 records · Page 14
All sourcesNASA NTRSDOE OSTI
DOE OSTI2025

Influence of Steric and Electronic Properties of P2 Groups on Covalent Inhibitor Binding to SARS-CoV-2 Main Protease

The main protease (MPro) of SARS-CoV-2 is a critical enzyme required for viral replication, making it a prime target for antiviral drug development. Covalent inhibitors, which form a stable interaction with the catalytic C145, have demonstrated strong inhibition of MPro, but the influence of steric and electronic properties of P2 substituents, designed to engage the S2 substrate-binding subsite within the MPro active site, on inhibitor binding affinity remains underexplored. Here, in this study, we design and characterize two hybrid covalent inhibitors, BBH-3 and BBH-4, and present their X-ray crystallographic structures in complex with MPro, providing molecular insights into how their distinct P2 groups, a dichlorobenzyl moiety in BBH-3 and an adamantyl substituent in BBH-4, affect binding conformation and active site adaptability. Comparative structural analyses with previously characterized inhibitors, including BBH-2 and Mcule-5948770040, reveal how the P2 bulkiness and electronic properties influence active site dynamics, particularly through interactions with the S2 and S5 subsites. The P2 group of BBH-3 induces conformational shifts in the S2 helix and the S5 loop, while BBH-4 displaces M49, stabilizing its binding through hydrophobic interactions. Isothermal titration calorimetry further elucidates the impact of P2 modifications on inhibitor affinity, revealing a delicate balance between enthalpic and entropic contributions. The data demonstrate that BBH-3 exhibits less favorable binding, affirming that dichlorobenzyl substitution at the P2 position has a more negative impact on the affinity for MPro than bulky saturated cyclic groups. This underscores the feature that MPro active site malleability may be accompanied by a conformational strain.

SARS-CoV-2↗
DOE OSTI2025

Selective Binding and Light-Driven Release of Fluorous PF 6 – and Radioactive 99 TcO 4 – Anions for All-to-Nothing Liquid–Liquid Extraction

The removal of anions from aqueous media using molecular receptors in liquid–liquid extraction is a long-standing strategy to clean up contaminated water sources. Therein, high selectivity is needed to remove specific ions from mixtures of other ions, and high affinity provides extractions at low concentrations. However, the high affinity creates a conundrum by impeding the release of the ions in any stripping steps needed for further processing. To circumvent this problem, light-responsive receptors have been proposed as candidates for turning off the binding, but they are currently untested in liquid–liquid extraction. We tested the feasibility of light-driven release using a cyanostar macrocycle. We demonstrate the selective extraction of PF$^{–}_{6}$ anions over large excesses of competing anions (Cl – , NO$^{–}_{3}$, SO$^{2–}_{4}$) followed by photodriven release for quantitative isolation of the target. Release relies on photoisomerization of the macrocycle’s five stilbenes generating distorted isomers to turn off binding. With modest reversibility, only a single-shot release was demonstrated, akin to photodriven uncaging. These methods were extended to the capture and photodriven release of ReO$^{–}_{4}$ and radioactive 99 TcO$^{–}_{4}$ anions at ∼90% efficiency. Extraction was demonstrated down to the highly dilute 4 ppb levels of the 99 TcO$^{–}_{4}$ anion. Furthermore, this proof-of-concept demonstration verifies the use of a large change in affinity for the all-to-nothing capture and release of target anions between liquid phases.

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

An artificial intelligence accelerated virtual screening platform for drug discovery

Abstract Structure-based virtual screening is a key tool in early drug discovery, with growing interest in the screening of multi-billion chemical compound libraries. However, the success of virtual screening crucially depends on the accuracy of the binding pose and binding affinity predicted by computational docking. Here we develop a highly accurate structure-based virtual screen method, RosettaVS, for predicting docking poses and binding affinities. Our approach outperforms other state-of-the-art methods on a wide range of benchmarks, partially due to our ability to model receptor flexibility. We incorporate this into a new open-source artificial intelligence accelerated virtual screening platform for drug discovery. Using this platform, we screen multi-billion compound libraries against two unrelated targets, a ubiquitin ligase target KLHDC2 and the human voltage-gated sodium channel Na V 1.7. For both targets, we discover hit compounds, including seven hits (14% hit rate) to KLHDC2 and four hits (44% hit rate) to Na V 1.7, all with single digit micromolar binding affinities. Screening in both cases is completed in less than seven days. Finally, a high resolution X-ray crystallographic structure validates the predicted docking pose for the KLHDC2 ligand complex, demonstrating the effectiveness of our method in lead discovery.

Science & Technology - Other Topics↗
DOE OSTI2021

Optoelectronic property comparison for isostructural Cu 2 BaGeSe 4 and Cu 2 BaSnS 4 solar absorbers

To target mitigation of anti-site defect formation in Cu 2 ZnSnS 4–x Se x , a new class of chalcogenides, for which Ba or Sr (group 2) replace Zn (group 12), has recently been introduced for prospective solar absorber application. Cu 2 BaGeSe 4 (CBGSe) and Cu 2 BaSnS 4 (CBTS) are two such compounds, which share a common trigonal crystal structure (P3 1 space group) and similar quasi-direct band gap (~2 eV). While CBTS-based films have already been studied, there are no reports yet on films and solar cells based on related CBGSe. To identify key differences and similarities in the electronic properties between these two materials, electronic characteristics (e.g., carrier concentration, mobility, electron affinity, defect levels, recombination, and charge carrier kinetics) of vacuum-deposited CBGSe and CBTS films are compared using a variety of characterization methods. Hall effect measurements reveal that CBGSe films have relatively higher hole carrier concentration and lower mobility (3 × 10 15 cm –3 , 0.6 cm 2 V –1 s –1 ) compared to CBTS (5 × 10 12 cm –3 , 3.5 cm 2 V –1 s –1 ). Photoelectron spectroscopy yields low electron affinity values for both CBGSe (3.7 eV) and CBTS (3.3 eV), pointing to the necessity of pursuing low electron affinity buffer materials for both types of absorbers. At low temperatures, CBGSe films show free-exciton photoluminescence, as well as pronounced deep-level emission at ~1.4 eV, while CBTS films exhibit a strong bound-exciton signal with noticeably less intense deep-level emission than for CBGSe. Charge carrier kinetics, transport, and recombination properties of both types of films are also analyzed using optical-pump terahertz-probe spectroscopy and time-resolved microwave conductivity. The first CBGSe prototype solar cells (using chemical bath deposited CdS as a buffer layer) show a maximum of 1.5% efficiency with ~0.62 V open-circuit voltage. Furthermore, the measured properties point to possible limiting factors for CBGSe and related films for PV and optoelectronics and provide insights on possible approaches for improvement within this multinary chalcogenide family.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2022

Designing 1D multiheme peptide amphiphile assemblies reminiscent of natural systems

We discuss protein assemblies that bind and organize ordered arrays of cofactors yield function structures. Multiheme assemblies found in nature yield electronically conductivity 1D nanoscale fibers and are employed in anaerobic respiration. To understand the fundamental characteristics of these organized arrays, the design of peptide amphiphiles that assemble into 1D nanostructures and yield metalloporphyrin binding sites is presented. One challenge with this class of peptide amphiphiles is identifying the correct sequence composition for high affinity binding with high heme density. Here, the peptide c16-AH(Kx)n-CO 2 H is explored to identify the impact of sequence length (n) and amino acid identity (x = L, I, or F) on binding affinity and midpoint potential. When n = 2, the peptide assembly yields the greatest affinity. The resulting nanoscale assemblies yield ordered arrays of the redox active molecule heme and have potential utility in the development of supramolecular bioelectronic materials useful in sensing as well as the development of enzymatic materials.

77 NANOSCIENCE AND NANOTECHNOLOGY↗
DOE OSTI2023

Structural and biochemical characterisation of Co 2+ -binding sites on serum albumins and their interplay with fatty acids

Serum albumin–Co 2+ interactions are of clinical importance. They play a role in mediating the physiological effects associated with cobalt toxicity and are central to the albumin cobalt binding (ACB) assay for diagnosis of myocardial ischemia. To further understand these processes, a deeper understanding of albumin–Co 2+ interactions is required. Here, we present the first crystallographic structures of human serum albumin (HSA; three structures) and equine serum albumin (ESA; one structure) in complex with Co 2+ . Amongst a total of sixteen sites bearing a cobalt ion across the structures, two locations were prominent, and they relate to metal-binding sites A and B. Site-directed mutagenesis and isothermal titration calorimetry (ITC) were employed to characterise sites on HSA. The results indicate that His9 and His67 contribute to the primary (putatively corresponding to site B) and secondary Co 2+ -binding sites (site A), respectively. The presence of additional multiple weak-affinity Co 2+ binding sites on HSA was also supported by ITC studies. Furthermore, addition of 5 molar equivalents of the non-esterified fatty acid palmitate (C16:0) reduced the Co 2+ -binding affinity at both sites A and B. The presence of bound myristate (C14:0) in the HSA crystal structures provided insight into the fatty acid-mediated structural changes that diminish the affinity of the protein toward Co 2+ . Together, these data provide further support for the idea that ischemia-modified albumin corresponds to albumin with excessive fatty-acid loading. Collectively, our findings provide a comprehensive understanding of the molecular underpinnings governing Co 2+ binding to serum albumin.

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

From small changes to big gains: pyridinium-based tetralactam macrocycle for enhanced sugar recognition in water

The complex distribution of functional groups in carbohydrates, coupled with their strong solvation in water, makes them challenging targets for synthetic receptors. Despite extensive research into various molecular frameworks, most synthetic carbohydrate receptors have exhibited low affinities, and their interactions with sugars in aqueous environments remain poorly understood. In this work, we present a simple pyridinium-based hydrogen-bonding receptor derived from a subtle structural modification of a well-known tetralactam macrocycle. This small structural change resulted in a dramatic enhancement of glucose binding affinity, increasing from 56 M −1 to 3001 M −1 . Remarkably, the performance of our synthetic lectin surpasses that of the natural lectin, concanavalin A, by over fivefold. X-ray crystallography of the macrocycle–glucose complex reveals a distinctive hydrogen bonding pattern, which allows for a larger surface overlap between the receptor and glucose, contributing to the enhanced affinity. Furthermore, this receptor possesses allosteric binding sites, which involve chloride binding and trigger receptor aggregation. This unique allosteric process reveals the critical role of structural flexibility in this hydrogen-bonding receptor for the effective recognition of sugars. We also demonstrate the potential of this synthetic lectin as a highly sensitive glucose sensor in aqueous solutions.

Zhai, Canjia↗
DOE OSTI2020

Comparing GGA, GGA+ U , and meta-GGA functionals for redox-dependent binding at open metal sites in metal–organic frameworks

Metal–organic frameworks (MOFs) with open metal sites have been widely investigated for the selective adsorption of small molecules via redox mechanisms where charge transfer can take place between the binding site and the adsorbate of interest. Quantum-chemical screening methods based on density functional theory have emerged as a promising route to accelerate the discovery of MOFs with enhanced binding affinities toward various adsorbates. However, the success of this approach is linked to the accuracy of the underlying density functional approximations (DFAs). In this work, we compare commonly used generalized gradient approximation (GGA), GGA+U, and meta-GGA exchange-correlation functionals in modeling redox-dependent binding at open metal sites in MOFs using O 2 and N 2 as representative small molecules. We find that the self-interaction error inherent to the widely used Perdew, Burke, and Ernzerhof (PBE) GGA predicts metal sites that are artificially redox-active, as evidenced by their strong binding affinities, short metal–adsorbate bond distances, and large degree of charge transfer. The incorporation of metal-specific, empirical Hubbard U corrections based on the transition metal oxide literature systematically reduces the redox activity of the open metal sites, often improving agreement with experiment. Additionally, the binding behavior shifts from strong chemisorption to weaker physisorption as a function of U. The M06-L meta-GGA typically predicts binding energies between those of PBE-D3(BJ) and PBE-D3(BJ)+U when using empirically derived U values from the transition metal oxide literature. Despite the strong sensitivity of the binding affinities toward a given DFA, the GGA, GGA+U, and meta-GGA approaches often yield the same qualitative trends and structure–property relationships.

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

Anion photoelectron spectroscopy and chemical bonding of ThS 2 – and ThSO –

Anion photoelectron spectra of ThSO – and ThS 2 – were recorded using the third (355 nm) harmonic of an Nd-YAG laser; these provided the measured vertical detachment energies of each anion. The experiments are supported by extensive coupled cluster calculations on ThSO, ThSO – , ThS 2 , and ThS 2 – , as well as the oxygen congeners ThO 2 and ThO 2 – . The ab initio calculations, which included complete basis set extrapolations, spin–orbit effects using four-component coupled cluster, and higher-order correlation contributions through CCSDT(Q), yielded an adiabatic electron affinity for ThO 2 – that was within 0.02 eV of the previously determined experimental value. The singly occupied molecular orbital (SOMO) in all three anions corresponds primarily to the 7s orbital on Th. Successive substitution of S for each O in ThO 2 leads to larger electron affinities and smaller bond angles in the neutral molecules, but larger angles in the anions. As demonstrated by Franck–Condon simulations of the spectra using the CCSD(T) spectroscopic constants, substitution of O by S significantly complicates the resulting detachment spectra due to the lower vibrational frequencies in the sulfur species. Altogether the calculated vertical detachment energies are in very good agreement with the experiment. In addition to the adiabatic electron affinities of each species, atomization energies and heats of formation have also been determined via the FPD approach with expected uncertainties of 1–2 kcal/mol.

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

Conformation-specific inhibitors of activated Ras GTPases reveal limited Ras dependency of patient-derived cancer organoids

The small GTPases H, K, and NRAS are molecular switches indispensable for proper regulation of cellular proliferation and growth. Several mutations in the genes encoding members of this protein family are associated with cancer and result in aberrant activation of signaling processes caused by a deregulated recruitment of downstream effector proteins. In this study, we engineered variants of the Ras-binding domain (RBD) of the C-Raf proto-oncogene, Ser/Thr kinase (CRAF). These variants bound with high affinity with the effector-binding site of Ras in an active conformation. Structural characterization disclosed how the newly identified RBD mutations cooperate and thereby enhance affinity with the effector-binding site in Ras compared with WT RBD. The engineered RBD variants closely mimicked the interaction mode of naturally occurring Ras effectors and acted as dominant-negative affinity reagents that block Ras signal transduction. We report experiments with cancer cells showed that expression of these RBD variants inhibits Ras signaling, reducing cell growth and inducing apoptosis. Using these optimized RBD variants, we stratified patient-derived colorectal cancer organoids with known Ras mutational status according to their response to Ras inhibition. These results revealed that the presence of Ras mutations was insufficient to predict sensitivity to Ras inhibition, suggesting that not all of these tumors required Ras signaling for proliferation. In summary, by engineering the Ras/Raf interface of the CRAF-RBD, we identified potent and selective inhibitors of Ras in its active conformation that outcompete binding of Ras-signaling effectors.

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

Multimeric antibodies from antigen-specific human IgM+ memory B cells restrict Plasmodium parasites

Multimeric immunoglobulin-like molecules arose early in vertebrate evolution, yet the unique contributions of multimeric IgM antibodies to infection control are not well understood. This is partially due to the difficulty of distinguishing low-affinity IgM, secreted rapidly by plasmablasts, from high-affinity antibodies derived from later-arising memory cells. We developed a pipeline to express B cell receptors (BCRs) from Plasmodium falciparum–specific IgM+ and IgG+ human memory B cells (MBCs) as both IgM and IgG molecules. BCRs from both subsets were somatically hypermutated and exhibited comparable monomeric affinity. Crystallization of one IgM+ MBC-derived antibody complexed with antigen defined a linear epitope within a conserved Plasmodium protein. In its physiological multimeric state, this antibody displayed exponentially higher antigen binding than a clonally identical IgG monomer, and more effectively inhibited P. falciparum invasion. Forced multimerization of this IgG significantly improved both antigen binding and parasite restriction, underscoring how avidity can alter antibody function. This work demonstrates the potential of high-avidity IgM in both therapeutics and vaccines.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2026

Short and medium range structure in elastic deformation of metallic and covalent glasses

Here, we present a concise methodology to analyze structural response to the applied stress in amorphous solids, including metallic glasses (MG), glassy selenium, silica and polycarbonate, using high energy x-ray diffraction and atomic pair distribution function (PDF) analysis. To assess the structural anisotropy induced by applied axial stress, diffraction data were expanded into spherical harmonics. Using Bessel transformation, components of the structure function were converted into isotropic and anisotropic PDFs. The PDFs were compared to the expected model behavior for ideal elastic deformation to separate homogeneous affine strain from local non-affine strains. In metallic glass the range of non-affine deformation is limited to the nearest neighbor shell, suggesting local strain relaxation under stress that occurs even in the elastic regime. Beyond the second atomic shell strain is uniform. However, in glassy silica, polycarbonate and selenium strong local bonding inhibits local displacements and strain in short range order is accommodated by rotation of local units. Interestingly, beyond a molecular unit, deformation in covalent systems is similar to MG, and response of the medium range order scales with the macroscopic stress.

glassy structure↗
DOE OSTI2020

Recognition of nuclear export signals by CRM1 carrying the oncogenic E571K mutation

The E571K mutation of CRM1 is highly prevalent in some cancers, but its mechanism of tumorigenesis is unclear. Glu571 of CRM1 is located in its nuclear export signal (NES)-binding groove, suggesting that binding of select NESs may be altered. We generated HEK 293 cells with either monoallelic CRM1WT/E571K or biallelic CRM1E571K/E571K using CRISPR/Cas9. We also combined analysis of binding affinities and structures of 27 diverse NESs for wild-type and E571K CRM1 with structure-based bioinformatics. While most NESs bind the two CRM1 similarly, NESs from Mek1, eIF4E-transporter, and RPS2 showed >10-fold affinity differences. These NESs have multiple charged side chains binding close to CRM1 position 571, but this feature alone was not sufficient to predict different binding to CRM1(E571K). Consistent with eIF4E-transporter NES binding weaker to CRM1(E571K), eIF4E-transporter was mislocalized in tumor cells carrying CRM1(E571K). This serves as proof of concept that understanding how CRM1(E571K) affects NES binding provides a platform for identifying cargoes that are mislocalized in cancer upon CRM1 mutation. Finally, we showed that large affinity changes seen with some NES peptides (of Mek1 and RPS2) do not always translate to the full-length cargoes, suggesting limitations with current NES prediction methods. Therefore, comprehensive studies like ours are imperative to identify CRM1 cargoes with real pathogenic potential.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Distinct function of Chlamydomonas CTRA-CTR transporters in Cu assimilation and intracellular mobilization

Abstract Successful acclimation to copper (Cu) deficiency involves a fine balance between Cu import and export. In the green alga Chlamydomonas reinhardtii, Cu import is dependent on a transcription factor, Copper Response Regulator 1 (CRR1), responsible for activating genes in Cu-deficient cells. Among CRR1 target genes are two Cu transporters belonging to the CTR/COPT gene family (CTR1 and CTR2) and a related soluble protein (CTR3). The ancestor of these green algal proteins was likely acquired from an ancient chytrid and contained conserved cysteine-rich domains (named the CTR-associated domains, CTRA) that are predicted to be involved in Cu acquisition. We show by reverse genetics that Chlamydomonas CTR1 and CTR2 are canonical Cu importers albeit with distinct affinities, while loss of CTR3 did not result in an observable phenotype under the conditions tested. Mutation of CTR1, but not CTR2, recapitulates the poor growth of crr1 in Cu-deficient medium, consistent with a dominant role for CTR1 in high-affinity Cu(I) uptake. On the other hand, the overaccumulation of Cu(I) (20 times the quota) in zinc (Zn) deficiency depends on CRR1 and both CTR1 and CTR2. CRR1-dependent activation of CTR gene expression needed for Cu over-accumulation can be bypassed by the provision of excess Cu in the growth medium. Over-accumulated Cu is sequestered into the acidocalcisome but can become remobilized by restoring Zn nutrition. This mobilization is also CRR1-dependent, and requires activation of CTR2 expression, again distinguishing CTR2 from CTR1 and consistent with the lower substrate affinity of CTR2. One sentence summary Regulation of Cu uptake and sequestration by members of the CTR family of proteins in Chlamydomonas.

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

Structures of the mitochondrial single-stranded DNA binding protein with DNA and DNA polymerase γ

Abstract The mitochondrial single-stranded DNA (ssDNA) binding protein, mtSSB or SSBP1, binds to ssDNA to prevent secondary structures of DNA that could impede downstream replication or repair processes. Clinical mutations in the SSBP1 gene have been linked to a range of mitochondrial disorders affecting nearly all organs and systems. Yet, the molecular determinants governing the interaction between mtSSB and ssDNA have remained elusive. Similarly, the structural interaction between mtSSB and other replisome components, such as the mitochondrial DNA polymerase, Polγ, has been minimally explored. Here, we determined a 1.9-Å X-ray crystallography structure of the human mtSSB bound to ssDNA. This structure uncovered two distinct DNA binding sites, a low-affinity site and a high-affinity site, confirmed through site-directed mutagenesis. The high-affinity binding site encompasses a clinically relevant residue, R38, and a highly conserved DNA base stacking residue, W84. Employing cryo-electron microscopy, we confirmed the tetrameric assembly in solution and capture its interaction with Polγ. Finally, we derived a model depicting modes of ssDNA wrapping around mtSSB and a region within Polγ that mtSSB binds.

Biochemistry & Molecular Biology↗
DOE OSTI2024

Stereoselective recognition of morphine enantiomers by μ -opioid receptor

Stereospecific recognition of chiral molecules plays a crucial role in biological systems. The μ-opioid receptor (MOR) exhibits binding affinity towards (-)-morphine, a well-established gold standard in pain management, while it shows minimal binding affinity for the (+)-morphine enantiomer, resulting in a lack of analgesic activity. Understanding how MOR stereoselectively recognizes morphine enantiomers has remained a puzzle in neuroscience and pharmacology for over half-a-century due to the lack of direct observation techniques. To unravel this mystery, we constructed the binding and unbinding processes of morphine enantiomers with MOR via molecular dynamics simulations to investigate the thermodynamics and kinetics governing MOR's stereoselective recognition of morphine enantiomers. Our findings reveal that the binding of (-)-morphine stabilizes MOR in its activated state, exhibiting a deep energy well and a prolonged residence time. In contrast, (+)-morphine fails to sustain the activation state of MOR. Furthermore, the results suggest that specific residues, namely D114 2.50 and D147 3.32 , are deprotonated in the active state of MOR bound to (-)-morphine. This work highlights that the selectivity in molecular recognition goes beyond binding affinities, extending into the realm of residence time.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2019

Plant roots stimulate the decomposition of complex, but not simple, soil carbon

Roots release carbon into soil and can alleviate energy limitation of microbial organic matter decomposition. We know little about the effects of roots on microbial decomposition of different organic matter substrates, despite the importance for soil carbon stocks and turnover. Through implementing root-microbe interactions, the Carbon, Organisms, Rhizosphere, and Protection in the Soil Environment (CORPSE) model was previously shown to represent dynamics of total soil carbon in temperate forest field experiments. However, the model permits alternative hypotheses concerning microbial-substrate affinity. We investigated how root inputs affect decomposition of soil organic carbon (SOC) with variable decomposability. We simulated SOC stocks in CORPSE and compared microbial degradation of two substrates types with varying root-microbe interactions under two alternative hypotheses that varied in microbial-substrate affinity. We compared our modeled hypotheses to a forest field experiment where we quantified decomposition of isotopically-labeled starch and leaf tissues in soils with manipulated root access to microbes. Here, we tested the hypothesis that decomposition of leaves would be more sensitive to root inputs than decomposition of starch, corresponding to the alternative model hypothesis. In the field study, leaf decomposition increased with root density while starch decomposition was unchanged by root density. Microbial biomass and enzyme activity consistently increased with root inputs in CORPSE and the field study. Our field experiment supported the CORPSE simulations with high microbial-substrate affinity. Roots stimulated microbial growth and enzyme production, which increased degradation of more complex substrates such as leaf tissues. Substrates that were easily decomposed, such as starch, may already be degrading at a maximum rate in the absence of rhizosphere influence because their decomposition rate was unchanged by root inputs. We found that the degree to which roots stimulate microbial decomposition depends on the substrate being decomposed, and that root-microbe interactions influenced SOC stocks in both our model and field experiment. Environmental changes that alter root-microbe interactions could, therefore, alter soil C stocks and biogeochemical cycling, and models of these interactions should incorporate differential influence of rhizosphere inputs on different substrates.

59 BASIC BIOLOGICAL SCIENCES↗