The Journal of Physical Chemistry B最新文献

{"title":"Capturing Spatial Covariance for Efficient Multipolar Electrostatic Parameterization in DNA via Multioutput Learning","authors":"Zhenyu Liu,&nbsp;Yongna Yuan,&nbsp;Ruisheng Zhang,&nbsp;Wei Su","doi":"10.1021/acs.jpcb.6c04920","DOIUrl":"https://doi.org/10.1021/acs.jpcb.6c04920","url":null,"abstract":"<p>In DNA force field development, introducing high-rankatomic multipolemoments (AMMs) to describe electron cloud anisotropy improves theaccuracy of electrostatic energy calculations. However, high-rankAMMs have many components. Existing machine learning methods usuallymodel each component independently, which increases model size andcomputational cost. This approach ignores the correlations among componentsand cannot balance accuracy and efficiency. In this study, a DNA molecularelectrostatic energy data set was constructed for six base pairingtypes to obtain AMMs labels up to the hexadecapole moment. We evaluatedtwo task grouping strategies alongside three multioutput Gaussianprocess regression (MOGPR) architectures (the Linear Model of Coregionalization(LMC), Intrinsic Coregionalization Model (ICM), and SemiparametricLatent Factor Model (SLFM)). Results showed that the Component strategy,which groups components by rank, reduced the total number of modelsby 80% for each data set. This grouping lowered the computationaland maintenance costs of force field construction while reducing interferencebetween components of different ranks. Among the MOGPR architectures,SLFM balanced accuracy and efficiency. It described the spatial covariancerelationships among tasks through a low-rank structure, overcomingthe limitations of independent prediction. In molecular electrostaticenergy reconstruction, SLFM showed an even greater advantage. On theCG data set, which has high conformational dispersion, the mean absoluteerror of SLFM decreased by 46.5% compared with the single-task method.This study combined quantum chemical topology and multitask learning,providing a reference for predicting high-rank AMMs and developingDNA force fields.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":"130 39","pages":"10222–10232"},"PeriodicalIF":3.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149124694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Linear-Response and State-Specific Polarizable Continuum Models Yield Different ESIPT Tautomer Geometries of Flavonoid Anions","authors":"Qin Yu,&nbsp;Xiya Peng,&nbsp;Binghan Li,&nbsp;Fengling Mei,&nbsp;Jian Luo","doi":"10.1021/acs.jpcb.6c04063","DOIUrl":"https://doi.org/10.1021/acs.jpcb.6c04063","url":null,"abstract":"<p>The linear-response polarizable continuum model (LR-PCM)is routinelyused to optimize excited-state geometries in ESIPT systems, followedby single-point energy corrections with the state-specific PCM (SS-PCM).This mixed protocol implicitly assumes that the LR-PCM minimum coincideswith the minimum on the SS-PCM potential energy surface (PES)─anassumption that has never been systematically scrutinized in ESIPTsystems. Here, we investigate this question using two flavonoid anions(API-B4 and LUT-B4-α/β) with zero, one, or two explicitwater molecules hydrogen-bonded to the C4′–O^– group. By constructing one-dimensional potential energy curves alongthe O5–H proton-transfer coordinate, we compare LR-PCM andSS-PCM descriptions. The ESIPT barrier is found to be nearly identicalbetween the two models (differences &lt; 0.5 kcal/mol) and largelyinsensitive to explicit waters. Each explicit water molecule raisesthe S₁ excitation energies by about 0.1 eV by stabilizingthe HOMO more than the LUMO. More importantly, the keto minimum obtainedwith LR-PCM is not always a minimum on the SS-PCM PES. This discrepancyis correlated with the substantial increase in the excited-state dipolemoment induced by SS-PCM and is consistently reproduced across threehybrid functionals (ωB97X-D, CAM-B3LYP, M062X). Overall, thiswork provides new insight into the role of the SS-PCM-enhanced excited-statedipole moment in emission energy calculations.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":"130 39","pages":"10291–10297"},"PeriodicalIF":3.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149100837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-Equilibrium Dynamics of the Time-Dependent Excitonic Coupling in Fluorescent Protein Dimers","authors":"Robson Christie,&nbsp;Cerys Murray,&nbsp;Youngchan Kim,&nbsp;Jaewoo Joo","doi":"10.1021/acs.jpcb.6c05048","DOIUrl":"10.1021/acs.jpcb.6c05048","url":null,"abstract":"<p>We quantify the excitonic coupling in the homodimer ofthe dimericVenus fluorescent protein using a quantum-classical hybrid workflow.Because the anionic chromophore carries appreciable double-excitationcharacter, we obtain its site energy from domain-based local-pair-natural-orbitalsimilarity-transformed equation-of-motion coupled-cluster theory (DLPNO-STEOM-CCSD),which places the in-protein bright ππ* state at 523.90nm, in good agreement with the experimental absorption maximum near515 nm and validated against an explicit triples-corrected EOM-CCSD(fT)benchmark; single-excitation time-dependent density functional theory(TDDFT) blueshifts this state. Applying a transition-density coupling(TDC) formalism to the STEOM transition density and simulating theVenusA206 tandem-dimer construct (two β-barrels covalently joinedby an inter-domain linker), the covalent tether holds the A206 interfacedocked throughout 1 ns of room-temperature dynamics. We obtain a thermallyaveraged coupling of <em>J</em> = 32.8 ± 1.6 cm^–1 across the 1000-frame trajectory (Davydov splitting 2|<em>J</em>| = 65.6 ± 3.1 cm^–1), representing a 19% near-fieldenhancement over the ensemble point-dipole estimate (<em>J</em>_PDA = 27.6 ± 1.3 cm^–1) at the 24.69± 0.32 Å chromophore centroid separation. Furthermore, weargue that a separation of time scales resolves the apparent theoreticaltension between intermediate experimental excitonic couplings andthe highly decoherent biological environment. While it has been hypothesizedthat the fluorescent protein β-barrel scaffold sustains couplingby shielding the chromophore from thermal fluctuations, we emphasizethat the separation of time scales applies irrespective of the exactdegree of environmental decoherence and dissipation. Collective photoexcitationimprints the Davydov splitting under optical-limit dielectric screeningupon absorption, preceding bulk solvent relaxation and sub-picosecondenvironmental dephasing. To characterize the subsequent post-absorptionevolution, we employ stochastic wavefunction simulations to modelthe transition from a delocalized exciton superposition to incoherenthopping between localized chromophore states.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":"130 39","pages":"10233–10243"},"PeriodicalIF":3.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149014904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multifaceted Computational Analysis of O6-Methylguanine and O6-Methylthioguanine Nucleobase Complexes","authors":"Michael C. Bowman,&nbsp;Kirsten M. Stinson","doi":"10.1021/acs.jpcb.6c04517","DOIUrl":"https://doi.org/10.1021/acs.jpcb.6c04517","url":null,"abstract":"<p>Improper DNA methylation yields <em>O</em>⁶-methylguanine,which induces GC-AT mutations if left unchecked by <em>O</em>⁶-methylguanine DNA methyltransferase (MGMT). Previousab initio studies have computed the interaction energy of <em>O</em>⁶-methylguanine with cytosine and thymine, butthis study probes deeper by investigating the noncovalent interactionsthrough various forms of energy decomposition analysis. The same methodsare then applied to the sulfur analog of <em>O</em>⁶-methylguanine, <em>S</em>⁶-methylthioguanine,which is likewise highly mutagenic but has received considerably lesscomputational treatment. Interaction energies computed at the ωB97X-D3/aug-cc-pVTZand SAPT2+/aug-cc-pVDZ levels of theory revealed that <em>O</em>⁶-methylguanine and <em>S</em>⁶-methylthioguanineform substantially weaker complexes than the unmethylated G:C andTG:C pairs yet may continue to prefer binding to cytosine over thymine.NCI and NBO analyses demonstrated that the <em>O</em>⁶-methylguanine and <em>S</em>⁶-methylthioguaninecomplexes with cytosine or thymine are driven primarily by two hydrogenbonds, which are noticeably weaker than the average hydrogen bondobserved among the canonical base pairs. The molecular electrostaticpotential (MEP) of these nucleobases likewise predicted that the exocyclicamine on <em>O</em>⁶-methylguanine and <em>S</em>⁶-methylthioguanine is less electrophilic thanthe H-bond donors on guanine and thioguanine. In direct comparisonto <em>O</em>⁶-methylguanine, the <em>S</em>⁶-methylthioguanine complexes are qualitatively similarbut exhibit weaker hydrogen bonding and greater dispersion forces.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":"130 39","pages":"10192–10205"},"PeriodicalIF":3.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149093672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dissecting Hydrophobic and Hydrogen-Bonding Contributions in the Rim Binding of Pyromellitic Diimides to β-Cyclodextrin","authors":"Saranya C. Sasi,&nbsp;Sneha Anna Sunny,&nbsp;Akhil K. Sivan,&nbsp;Renjith Thomas,&nbsp;Retheesh Krishnan","doi":"10.1021/acs.jpcb.6c04529","DOIUrl":"https://doi.org/10.1021/acs.jpcb.6c04529","url":null,"abstract":"<p>Therelative contributions of hydrophobic interactions and hydrogenbonding in cyclodextrin host–guest systems remain a fundamentalchallenge in supramolecular chemistry. In the present study, a seriesof pyromellitic diimide (PMDI) derivatives bearing alkyl substituentsof different sizes was employed to investigate the origin of rim-bindinginteractions with β-cyclodextrin (β-CD). NMR, ROESY andICD studies established that PMDIs interact with β-CD throughthe narrow rim, with the alkyl substituents penetrating the cavity.The PMDI chromophore remained outside the cavity of the β-CD.In contrast, α-cyclodextrin (α-CD) complexes underwentshallow binding through their wider rim. The ¹³C NMR experimentsrevealed the presence of hydrogen-bonding interactions between PMDIcarbonyl oxygens and the primary hydroxyl groups of β-CD. DFTcalculations reproduced the experimentally observed binding geometriesfor both α- and β-CDs. NCI-RDG, NBO and QTAIM analysesconfirmed the coexistence of hydrogen-bonding and weak dispersive/vander Waals contacts that are structurally consistent with hydrophobicinclusion. The computational studies also showed that β-CD complexesexhibited stronger hydrogen bonds than the corresponding α-CDcomplexes. Temperature-dependent ITC revealed distinct thermodynamicsignatures for the two cyclodextrins. The α-CD complexes displayedsmall positive or near-zero heat-capacity changes and strongly entropy-drivenbinding, indicating shallow association dominated by solvent releaseand weak hydrophobic interactions. In contrast, β-CD complexesshowed a systematic transition from hydrogen-bond-dominated bindingfor H-PMDI to cooperative weak dispersive/van der Waals interactionsand hydrogen-bond stabilization for <em>tert</em>-butyl-substitutedPMDI. The heat-capacity changes and enthalpy–entropy compensationbehavior collectively demonstrated that the relative contributionsof hydrophobic interactions and hydrogen bonding can be tuned throughthe size of the alkyl substituent and the cyclodextrin cavity.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":"130 39","pages":"10361–10370"},"PeriodicalIF":3.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149093552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structure-Transport Relationships in Aqueous Fructose Solutions: A Combined Molecular Dynamics and NMR Diffusion Study","authors":"San Vo Vinh Phan,&nbsp;Xinyue Zhou,&nbsp;Gabriel D. Barbosa,&nbsp;Tran Thi Bao Le,&nbsp;Christopher M. A. Parlett,&nbsp;Xiaolei Fan,&nbsp;Carmine D’Agostino,&nbsp;Alberto Striolo","doi":"10.1021/acs.jpcb.6c04242","DOIUrl":"https://doi.org/10.1021/acs.jpcb.6c04242","url":null,"abstract":"<p>Fructose is widelyused in the food industry and is proposedasa sustainable biomass feedstock for chemical manufacturing. Upon dissolutionin water, it undergoes mutarotation into different tautomers, primarilyβ-<span>d</span>-fructopyranose (68%) and β-<span>d</span>-fructofuranose(22%), as well as into the linear keto <span>d</span>-fructose structure.Although present only in small amounts, the linear tautomer may alterdiffusion within aqueous media and porous catalytic materials. Toelucidate the structure-transport properties of aqueous solutionscontaining fructose, molecular dynamics (MD) simulations are combinedwith nuclear magnetic resonance (NMR) diffusion experiments. ClassicMD simulations are conducted at atomistic resolution using three differentforce fields. The NMR diffusion experiments are conducted in deuteratedwater to differentiate water from sugar peaks in the experimentalsignal. When the OPLS-AA force field is implemented, the MD simulateddiffusion coefficients, as well as bulk system densities, are consistentwith experiments, indicating the atomistic models are realistic. Interrogatingthe simulation trajectories confirms that fructose molecules aggregateinto clusters, which lowers the diffusion coefficients of both fructoseand water at high fructose concentration. Modest differences are observedin the mobility of the two cyclic tautomers, even in the presenceof the linear counterpart. Such insight into the structure and mobilityof fructose in bulk aqueous solutions across a range of concentrationsis paramount to understanding several industrial processes, for examplethose involved in catalytic biomass upgrading technologies.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":"130 39","pages":"10298–10309"},"PeriodicalIF":3.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149124818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond the Geometric Mean: A Monopole-Based Combining Rule for Hydrogen-Bonding Cross-Interactions","authors":"Chen-Yang Liu,&nbsp;Lin-Xue Han,&nbsp;Ya-Fei Yuan","doi":"10.1021/acs.jpcb.6c03060","DOIUrl":"https://doi.org/10.1021/acs.jpcb.6c03060","url":null,"abstract":"<p>Intermolecularinteractions govern the condensed-phase propertiesof substances as well as the thermodynamic behavior and phase equilibriaof solutions. A central challenge in the molecular thermodynamicsof mixing is the estimation of cross-interaction energies (ε_AB) between unlike molecules from the pure-substance propertiesvia combining rules─a task complicated by the vast number ofpossible mixtures and the experimental difficulty of directly measuringcross-interaction energies. Classical Berthelot geometric-mean combiningrules, originally derived for exchangeable van der Waals interactions,are inadequate for specific donor–acceptor interactions suchas hydrogen bonding. Hydrogen bonding is governed by two independentmolecular characteristics: donor and acceptor abilities (α andβ). Consequently, the self-association energy of a pure substanceis expressed as the product αβ, following a Coulombic-typeattraction principle. Crucially, hydrogen-bonding interactions betweentwo unlike molecules A and B are intrinsically asymmetric and non-exchangeable(A → B ≠ B → A) since each molecule possessesits own distinct α and β parameters. To address this,we propose a new combining rule in which the cross-association energyis evaluated as the sum of two cross-products: α_Aβ_B + α_Bβ_A. Thismodel treats hydrogen bonding as mediated by two opposing monopoles(single charges) rather than dipoles, which fundamentally distinguishesit from conventional single-energy-parameter approaches, where cross-associationenergies are derived directly from pure-component self-associationenergies. To implement the model, H-bonding strengths based on thedimensionless Kamlet–Taft H-bonding donor and acceptor parametersare converted into physically meaningful interaction energies. Theresulting framework enables the prediction of mixture thermodynamicproperties and enthalpies of mixing from pure-component parametersalone.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":"130 39","pages":"10279–10290"},"PeriodicalIF":3.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149124789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering Supramolecular Nucleopeptide-Based Hydrogel Formation through Unique Combination of NMR Methods and Molecular Dynamics Simulations","authors":"Corentin Boulogne,&nbsp;Jeremy Morere,&nbsp;Noée Sigalas,&nbsp;Paul Hoschtettler,&nbsp;Emmanuelle Bignon,&nbsp;Marie-Christine Averlant-Petit,&nbsp;Loïc Stefan,&nbsp;Sabine Bouguet-Bonnet,&nbsp;Carole Gardiennet","doi":"10.1021/acs.jpcb.6c03854","DOIUrl":"https://doi.org/10.1021/acs.jpcb.6c03854","url":null,"abstract":"<p>Nucleopeptide-based hydrogels are attracting growinginterest owingto their biocompatibility and wide range of applications, particularlyin biotechnology. Their enhanced versatility compared to purely peptide-basedsystems enables fine-tuning of macroscopic properties to meet specificrequirements. However, rational optimization of these materials requiresa thorough understanding of their atomic-scale organization, whichremains challenging due to the inherent nature of these amorphous,soft, and highly hydrated materials. In this context, nuclear magneticresonance (NMR) spectroscopy emerges as a powerful technique for gainingvaluable insights into both the isotropic and anisotropic phases ofthe samples. This work focuses on developing a unique combinationof NMR methodologies to characterize the structural and dynamicalparameters of these hydrogels. Fast-field cycling (FFC) NMR relaxometryis employed to probe the dynamical changes occurring during the gelationprocess and to elucidate the complex mechanisms driving the liquid-to-geltransition. Furthermore, solid-state NMR (ssNMR) experiments, performedon samples in protonated and deuterated solvents, provide key insightsinto the intermolecular interactions that structure the three-dimensionalgel network. Molecular dynamics (MD) simulations corroborate theseexperimental findings and assess the stability and prevalence of variousnoncovalent interactions, while shedding light on the role of Watson–Crickpairing during the initial oligomerization steps.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":"130 39","pages":"10337–10347"},"PeriodicalIF":3.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149124755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Intercalators on the Properties of DNA Analyzed by Molecular Dynamics Simulations","authors":"Hisashi Ishida,&nbsp;Hidetoshi Kono","doi":"10.1021/acs.jpcb.6c02297","DOIUrl":"https://doi.org/10.1021/acs.jpcb.6c02297","url":null,"abstract":"<p>Intercalation of small molecules between DNA base pairsaffectsDNA conformation, disrupting essential cellular processes, includingreplication, transcription, and repair. We investigated conformationalchanges in 18-mer DNA upon intercalation of doxorubicin, SYBR Gold,and YOYO-1 using extensive molecular dynamics simulations. Two mainpatterns for the intercalation were identified: RISE-type intercalationoccurs between adjacent base pairs and extends the DNA helix withdecreased twist angles, whereas BPEV-type intercalation proceeds throughbase-pair eversion without significant DNA extension. Kinetic analysisrevealed that association rates for intercalation followed the order:first YO moiety (monointercalation) &gt; SYBR Gold &gt; doxorubicin&gt; YOYO-1(bis-intercalation). The free energy landscape showed that forcesat DNA termini reached up to 117 pN during stretching. Notably, basepairs adjacent to intercalators were protected from strand separation,accompanied by additional helical unwinding. MM-GBSA/PBSA analysisrevealed that the driving force for intercalation is the stackingenergy, and the binding affinity was highest for minor-groove binding.Persistence length decreased with single-molecule binding but recoveredwith two molecules due to their electrostatic repulsion. Mechanicalproperties of intercalated DNA showed position dependence, demonstratingthat multiple intercalation modes coexist in solution. The heterogeneousnature of intercalation explains why experimental measurements reflectensemble averages, rather than single binding configurations.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":"130 39","pages":"10123–10139"},"PeriodicalIF":3.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149093615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electron Paramagnetic Resonance (EPR) Spectroscopy Reveals Nucleotide- and Partner-Dependent Conformational Ensembles in Hsp90","authors":"Christini Fiotaki,&nbsp;Daniella Goldfarb,&nbsp;Angeliki Giannouli","doi":"10.1021/acs.jpcb.6c03220","DOIUrl":"https://doi.org/10.1021/acs.jpcb.6c03220","url":null,"abstract":"<p>Heat shock protein 90 kDa (Hsp90) is an ATP-dependentmolecularchaperone whose function relies on conformational rearrangements andinteractions with cochaperones and clients. Binding of nucleotides,cochaperones, and clients leads to functional structural rearrangements,often associated with heterogeneous structural ensembles that arechallenging to characterize using high-resolution structure determinationmethods alone. Electron paramagnetic resonance (EPR) spectroscopyhas emerged as a powerful approach for tracking the conformationallandscape of proteins. However, despite its great potential, its applicationto Hsp90 homologs has so far remained limited, and the insights gainedhave not yet been comprehensively reviewed. In this mini-review, wesummarize EPR studies on cytosolic, mitochondrial, and endoplasmicreticulum Hsp90 with the aim of highlighting how EPR has advancedour understanding of nucleotide- and partner-dependent conformations.Specifically, we summarize how continuous wave EPR (CW-EPR), doubleelectron–electron resonance (DEER), and electron nuclear doubleresonance (ENDOR) spectroscopies revealed conformational equilibria,symmetry breaking, dissociation constants, and the structural roleof intrinsically disordered regions within Hsp90, while also discussingmethodological advances and recent extensions to cellular contexts.Overall, these studies establish EPR spectroscopy as a valuable biophysicaltool for resolving conformational ensembles and structural heterogeneityunderlying Hsp90’s function, with general relevance to thestructural biology, spectroscopy, and chaperone fields, and pave theway for future <em>in vitro</em> and in-cell investigationsof this exciting molecular chaperone.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":"130 38","pages":"9750–9763"},"PeriodicalIF":3.2,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149027896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}