The Journal of Physical Chemistry B最新文献

{"title":"How Alkali Metal Cations Affect the Structure and Reactivity of the Hydrated Dielectron","authors":"Tatiana Nemirovich,&nbsp;Pavel Jungwirth,&nbsp;Ondrej Marsalek","doi":"10.1021/acs.jpcb.6c04903","DOIUrl":"https://doi.org/10.1021/acs.jpcb.6c04903","url":null,"abstract":"<p>Hydrated electrons of opposite spins pair to form dielectronsatsufficiently high concentrations that can be achieved by dissolutionof alkali metals in water. While experimental investigations of thesesystems are challenging due to their vigorous, even explosive, reactivity,simulations open the possibility to characterize the structure andreactivity of hydrated dielectrons and the effects of alkali cationsthereon. Here, we present ab initio molecular dynamics simulationsof a hydrated dielectron with or without explicit Li⁺ orCs⁺ counterions. While the overall solvation structureis preserved in all these systems, the presence of cations has a distincteffect of increasing the dielectron gyration radius by about 6% andforming cation-specific cation−dielectron arrangements. Moreover,analysis of water bond lengths reveals in all studied systems a substantialelongation of first-shell O−H bonds oriented toward the dielectron,providing a structural explanation for vibrational red shifts observedin resonance Raman measurements. Finally, at the 10 ps simulationtime scale, rare reactive events were observed, albeit only for thesystem without metal cations, where hydride intermediates stable onpicosecond time scales were identified. These observations also suggestthat, on the investigated time scales, metal cations may suppresshydrated dielectron reactivity.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":"130 44","pages":"11875–11886"},"PeriodicalIF":3.2,"publicationDate":"2026-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149330356","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":"Migration Mechanism Regulated by the Coupling between Ions and Charged Nanoparticles in Janus Nanochannels","authors":"Junhao Pi,&nbsp;Anping Ji,&nbsp;Chenxi Yang,&nbsp;Zhenyu Yang,&nbsp;Songjie Liu,&nbsp;Siyu Xiang,&nbsp;Zhengwei Zhang,&nbsp;Yao Xiao,&nbsp;Yuange Jing,&nbsp;Xiong Chen,&nbsp;Guangyao Zhu","doi":"10.1021/acs.jpcb.6c04544","DOIUrl":"https://doi.org/10.1021/acs.jpcb.6c04544","url":null,"abstract":"<p>Charged nanoparticle migration through asymmetric nanochannelsis important for particle separation, nanoscale drug delivery, andnanofluidic regulation. However, in electrolyte solutions, particletransport is governed not only by the applied electric field or fixedchannel charges but also by local ion distributions, particle counterionclouds, and electro-osmotic responses. Here, a Janus nanochannel modelwas constructed, and molecular dynamics simulations investigated thetranslocation of positively charged nanoparticles through an asymmetricfixed-charge channel. Increasing the positive charge at the rightend increased particle residence time near the Janus interface andpositively charged gating region, promoted counterion enrichment aroundthe particle, and weakened local water flow assistance. Increasingthe salt concentration enhanced particle-local counterion enrichmentand altered gating-region charge compensation; the associated nonmonotonicmigration response is consistent with competition between these effects.A stronger applied electric field accelerated translocation and reducedparticle-local counterion screening but did not eliminate the retardationeffect of the right-half gating region. Particle-free channel simulationsfurther revealed ion enrichment and spatially nonuniform ion and watertransport near the fixed-charge polarity transition. These resultssuggest that fixed-charge gating, particle-local screening, gating-regioncharge compensation, and local electro-osmotic response jointly influencecharged particle migration in Janus nanochannels.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":"130 44","pages":"11819–11831"},"PeriodicalIF":3.2,"publicationDate":"2026-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149330303","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":"Contributions to Stability of H-Bonding and Stacking between Nucleic Acid Bases","authors":"Steve Scheiner","doi":"10.1021/acs.jpcb.6c06052","DOIUrl":"https://doi.org/10.1021/acs.jpcb.6c06052","url":null,"abstract":"<p>It is well-knownthat nucleic acid bases engage in complementaryG-C and A-T H-bonded pairs. Each such coplanar pair is positionedabove another such pair as separate rungs in a double-helical ladder.DFT calculations probe the separate contributions of the H-bondingwithin each rung and the stacking interactions between the rungs.Various tetramers are constructed by placing two complementary pairsabove one another, free of geometrical constraints imposed by thesugar–phosphate backbone. The H-bonding within each coplanarpair is found to be much more important than the stacking which inducesonly very minor perturbations of the geometries or energetics withineach coplanar H-bonded pair. There is very little cooperativity betweenthe two sorts of interactions.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":"130 44","pages":"11844–11851"},"PeriodicalIF":3.2,"publicationDate":"2026-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149330390","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":"Machine-Learning-Guided Identification of CCT245737 as a Functional Pan-G-Quadruplex Ligand for the Treatment of Multiple Myeloma","authors":"Jiawen Chu,&nbsp;Siqi Yu,&nbsp;Manqing Zhao,&nbsp;Yutong Ye,&nbsp;Mo Chen,&nbsp;Jian Gao","doi":"10.1021/acs.jpcb.6c05843","DOIUrl":"https://doi.org/10.1021/acs.jpcb.6c05843","url":null,"abstract":"<p>Multiple myeloma (MM) still lacks curative therapies,creatingan urgent demand for innovative agents targeting unique molecularvulnerabilities. G-quadruplex (G4) stabilization modulates oncogenicregulatory regions and displays potent preclinical antitumor effects.Nevertheless, most existing G4 ligands act on single G4 motifs. Pan-G4agents capable of perturbing multiple oncogenic pathways are scarce,while conventional high-throughput screening is costly and labor-intensive.Herein, we constructed a repurposing-driven screening pipeline combiningcurated fluorescence resonance energy transfer (FRET)-derived melting-temperatureshift (ΔTm) data sets, 1024-bit Chemistry Development Kit (CDK)molecular fingerprints, three machine-learning classifiers, and multi-G4molecular docking. In nested cross-validation, our Random Forest (RF)classifier yielded a receiver operating characteristic area underthe curve (ROC AUC) of 0.840 and a Matthews correlation coefficient(MCC) of 0.708, superior to label-randomized controls. Consensus screeningof 4270 compounds from the TargetMol Anticancer Library yielded 812high-confidence hits; the top-ranked 487 candidates underwent dockingagainst four structurally diverse oncogenic G4s (c-Myc, c-KIT, Bcl-2,k-RAS). CCT245737 ranked in the top ten across all four independentdocking analyses. Functional assays revealed that CCT245737 suppressedthe viability of U266 and RPMI-8226 MM cells (IC₅₀ = 0.58± 0.06 and 0.68 ± 0.04 μM) and enhanced nuclear BG4signals. FRET-melting and NMM-displacement assays verified its concentration-dependentstabilization of the four G4s with minimal duplex-DNA interference.qPCR and immunoblotting confirmed downregulation of c-Myc, c-KIT,Bcl-2, and k-RAS at both mRNA and protein levels. In summary, CCT245737is validated as a promising pan-G4 ligand, and our FRET-guided workflowoffers a feasible repurposing strategy for discovering anti-MM G4-targetedtherapeutics.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":"130 44","pages":"11942–11956"},"PeriodicalIF":3.2,"publicationDate":"2026-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149330407","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":"Histidine Tautomerism-Mediated Regulation of β-Hairpin Formation and Primary Nucleation in Amyloidogenic PrP(106–126) A117 V Peptides","authors":"Lisha Wang,&nbsp;Jing Li,&nbsp;Ahmed Altayib,&nbsp;Rongrong Zhu,&nbsp;Yue Sun,&nbsp;Hu Shi,&nbsp;Lizhen Gao","doi":"10.1021/acs.jpcb.6c03552","DOIUrl":"https://doi.org/10.1021/acs.jpcb.6c03552","url":null,"abstract":"<p>Histidinetautomerism is increasingly recognized as a subtle yetpowerful regulator of protein structural dynamics, yet its mechanisticrole in amyloid nucleation remains poorly understood. In current study,we investigate how histidine protonation states govern the early stageaggregation and primary nucleation of PrP(106–126) A117 V,a prion-related peptide whose mutation markedly accelerates oligomerformation and cytotoxicity. Using molecular dynamics simulations,we systematically characterized the conformational ensembles of monomersthrough tetramers across distinct histidine tautomeric states (δand ε). We find that tautomerism exerts minimal influence onβ-sheet propensity in monomers and dimers, but becomes decisiveat the trimer and tetramer level: the (δδε) trimeradopts a β-hairpin, while the (δεεε)tetramer harbors two β-hairpins that collectively define a nascentnucleation core. Based on these observations, we hypothesize a potentialtwo-step nucleation mechanism within the primary nucleation stage,in which structurally heterogeneous intermediates first accumulate,and one β-hairpin then serves as a template to recruit and organizea second, culminating in a β-hairpin-enriched nucleus. Our resultsestablish histidine tautomerism as a molecular switch that gates thetransition from disordered oligomers to ordered nuclei, offering aphysicochemical framework for understanding primary nucleation inprion and, more broadly, amyloidogenic systems.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":"130 44","pages":"11672–11680"},"PeriodicalIF":3.2,"publicationDate":"2026-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149330253","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":"Preparation Method Determines Valinomycin Organization and Phase Behavior in Charged Langmuir Monolayers","authors":"Amrita Chakraborty,&nbsp;Priyojit Das Gupta,&nbsp;Anabela Meier,&nbsp;Antara Roy,&nbsp;Saranya Pullanchery","doi":"10.1021/acs.jpcb.6c03977","DOIUrl":"https://doi.org/10.1021/acs.jpcb.6c03977","url":null,"abstract":"<p>Amphiphilic molecules are typically incorporated intolipid Langmuirmonolayers by two distinct methods: co-spreading, where lipid andamphiphile are deposited simultaneously, and injection, where theamphiphile is introduced into the aqueous subphase beneath a preformedmonolayer. Whether these methods produce equivalent molecular arrangementsremains an open question. Using valinomycin as a model ionophore,we investigate this question across lipid monolayers bearing anionic,zwitterionic, and cationic headgroups. Surface pressure–areaisotherms, fluorescence imaging, and vibrational sum-frequency generationspectroscopy together reveal that the two preparation methods producefundamentally different molecular organizations. Cospreading yieldsa uniform, well-incorporated monolayer, while injection produces akinetically trapped, spatially heterogeneous state in which valinomycinresides predominantly at the headgroup–water interface. Themagnitude of these differences scaled with lipid headgroup charge,implicating specific interactions between lipid headgroups and thecarbonyl-lined cavity of valinomycin as key determinants of the incorporationpathway. These findings establish that preparation history is a criticalparameter governing molecular organization in mixed amphiphile-lipidmonolayers.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":"130 44","pages":"11809–11818"},"PeriodicalIF":3.2,"publicationDate":"2026-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149330332","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":"Thermodynamic and Structural Basis of Selectivity in the Binding of Tetrapentylammonium to G-Quadruplexes","authors":"Xuan Li,&nbsp;David N. Dubins,&nbsp;James W. Wells,&nbsp;Tigran V. Chalikian","doi":"10.1021/acs.jpcb.6c05830","DOIUrl":"https://doi.org/10.1021/acs.jpcb.6c05830","url":null,"abstract":"<p>G-quadruplexesare an important class of noncanonical DNA structuresthat form from contiguous guanine repeats (G-tracts) and are implicatedin the regulation of genomic events. They are polymorphic in natureand, depending upon the orientation of their G-tracts, may fold intoa parallel, antiparallel, or hybrid topology. We previously foundthat tetraalkylammonium ions ([H(CH₂)_n]₄N⁺), despite their simplicity, bind to the parallelc-MYC G-quadruplex but not to the antiparallel human telomeric Tel22G-quadruplex or to duplex DNA. Within a homologous series of thesestructural minimalists, tetrapentylammonium (TPeA⁺) exhibitsthe highest affinity for the c-MYC G-quadruplex. The structure ofthe resulting stable complex has been solved by NMR. To discover theorigins of that selectivity, we examine here nine biologically relevantG-quadruplexes, which differ in sequence and topology, for the effectof TPeA⁺ on their melting temperatures, taken as a measureof thermal stability. The stoichiometry of binding, the binding constant,and the binding enthalpy were determined for each G-quadruplex, andthose thermodynamic parameters were related to the structural featuresof the G-quadruplexes. Binding of TPeA⁺ to all nine DNAsequences is driven by hydrophobic interactions, as indicated by theentropy-driven nature of the binding and by self-evident Coulombicinteractions between the positively charged ligand and polyanionicDNA. Selectivity is seen in binding constants that range from 40,500M^–1 for c-MYC to nil for Tel22. Comparisons withstructure indicate that binding is facilitated by unobstructed accessto the receiving G-quartet and favorable interactions with the flankingsequence. These results expand our understanding of the forces thatdirect the targeting of DNA, with implications for the developmentof tetraalkylammonium ions and their derivatives as a novel familyof topology-selective G-quadruplex-binding agents.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":"130 44","pages":"11779–11787"},"PeriodicalIF":3.2,"publicationDate":"2026-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149330349","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":"Co-Authorship and Keyword Networks in Five Decades of Molecular Simulation: A Network Analysis of a Scientific Publication Portfolio","authors":"Livia B. Pártay,&nbsp;Ottilia Fülöp,&nbsp;Béla Barabás","doi":"10.1021/acs.jpcb.6c05147","DOIUrl":"https://doi.org/10.1021/acs.jpcb.6c05147","url":null,"abstract":"<p>In the present paper, we illustrate and analyze the coauthorshipnetwork of publications authored by Michael L. Klein using standardsocial network analysis techniques. Beyond presenting and analyzingthe author-keyword network assigned to his publications, we also introduceabstract-similarity networks to enable a deeper and broader explorationof the relationships among Michael L. Klein’s publications.The resulting network structures and communities are also interpretedfrom a chemical perspective, highlighting recurring connections betweensimulation methodology, force-field development, and major applicationareas such as aqueous systems, lipid membranes, membrane proteins,and soft-matter self-assembly. More broadly, the study illustrateshow network-based approaches can be used to map the organization ofa large molecular simulation research program.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":"130 44","pages":"11832–11843"},"PeriodicalIF":3.2,"publicationDate":"2026-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149330379","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":"A Topological Framework for the Identification and Classification of Spanning Triplets in RNA–Protein Complexes","authors":"Raman Jangra,&nbsp;John F. Trant,&nbsp;Purshotam Sharma","doi":"10.1021/acs.jpcb.6c04239","DOIUrl":"https://doi.org/10.1021/acs.jpcb.6c04239","url":null,"abstract":"<p>Most functional RNA molecules interact with proteins.To betterunderstand these interactions, amino acid:ribonucleotide motifs ofdifferent sizes and scales need to be classified and characterized.Although pairs of amino acids and ribonucleotides have been previouslystudied, structural characteristics of triplets and other higher-orderspanning motifs present in RNA–protein complexes are not fullyunderstood. This is especially significant since such motifs may actas nexus points and provide a deeper understanding of RNA–proteinrecognition. To advance this goal, we propose a method for the automatedidentification of spanning triplet motifs in the crystal structuresof RNA–protein complexes using a topology-based classificationand nomenclature scheme. This method is also expandable to other higher-orderspanning motifs. Additionally, we investigate the frequency and compositionof spanning triplet motifs present in the available crystal structures.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":"130 44","pages":"11706–11717"},"PeriodicalIF":3.2,"publicationDate":"2026-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149330328","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":"Dissociative Electron Attachment in 1,3-Dimethyl-5-Thiocyanatouracil at Different Hydration Conditions","authors":"Adrian Szczyrba,&nbsp;Samanta Makurat,&nbsp;Vy T. T. Nguyen,&nbsp;Jiakuan Chen,&nbsp;Magdalena Datta,&nbsp;Karol Biernacki,&nbsp;Jaroslav Kočišek,&nbsp;Jozef Ďurana,&nbsp;Barbora Sedmidubská,&nbsp;Sebastian Demkowicz,&nbsp;Stephan Denifl,&nbsp;Janusz Rak","doi":"10.1021/acs.jpcb.6c05644","DOIUrl":"https://doi.org/10.1021/acs.jpcb.6c05644","url":null,"abstract":"<p>5-Thiocyanato-2′-deoxyuridine has emerged as apromisingradiosensitizer for cancer radiotherapy. Upon X-ray irradiation, hydratedelectrons generated in the tumor microenvironment can interact withthis molecule, forming reactive transient species capable of inducingdamage to DNA, the primary target of radiotherapy. In this work, weinvestigate dissociative electron attachment (DEA) to 1,3-dimethyl-5-thiocyanatouracil,a doubly methylated analogue of 5-thiocyanato-2′-deoxyuridine,in both the gas phase and microhydrated environments. Gas-phase measurementswere performed using a crossed electron–molecular beam apparatuscoupled with mass spectrometry, while microhydrated clusters wereexamined using a CLUster-Beam setup, enabling direct assessment ofhydration effects on DEA. The experimental results are supported byquantum chemical calculations, providing insight into thermodynamicand kinetic parameters, including electron affinities, reaction thresholds,and activation barriers. In both environments, the parent anion andthe CN^– fragment dominate the product distribution,accompanied by minor channels such as SCN^– formation.Microhydration leads to a moderate suppression of the S–CNbond cleavage pathway but does not inhibit the reaction. Overall,these findings demonstrate that microhydration modulates, yet preserves,DEA activity in this class of radiosensitizers, supporting their potentialeffectiveness under biologically relevant conditions.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":"130 44","pages":"11768–11778"},"PeriodicalIF":3.2,"publicationDate":"2026-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149330368","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}