Journal of Computational Chemistry最新文献

{"title":"How Do DICER1 Syndrome Mutations Disrupt Catalysis? Unveiling Dicer Metal Binding Architecture and Mechanism of Action Using MD Simulations and QM/MM Calculations","authors":"Dylan J. Nikkel,&nbsp;Stacey D. Wetmore","doi":"10.1002/jcc.70446","DOIUrl":"10.1002/jcc.70446","url":null,"abstract":"<p>The RNA interference (RNAi) pathway regulates gene expression and viral defense and has been harnessed in therapeutic solutions to inhibit otherwise undruggable proteins by preventing translation. Dicer initiates RNAi by generating cleaved RNA products that bind to a target mRNA to promote gene silencing. Mutations to the Dicer catalytic domain cause DICER1 syndrome, which increases the risk of cancers, including early childhood variants. However, the catalytic mechanism remains poorly defined due to the lack of structural data for Dicer bound to a substrate (or substrate mimic) in the presence of divalent ions known to be critical for nuclease activity. This study uses molecular dynamics (MD) simulations to uncover the first atomic level structure of the wild-type Dicer–RNA complex, including the binding pattern of two catalytically essential Mg²⁺ ions. Subsequently, quantum mechanics/molecular mechanics (QM/MM) techniques are used to elucidate the Dicer catalytic mechanism for phosphodiester bond cleavage. Among three fully characterized pathways, our data suggest catalysis is only feasible when both active site Mg²⁺ ions are directly coordinated to the RNA substrate and a hydroxide ion nucleophile is bound to an active site Mg²⁺ ion. Phosphodiester bond hydrolysis proceeds through a two-step mechanism involving a phosphorane intermediate that is stabilized by direct Mg²⁺–substrate coordination and a hydrogen bond with K1806. This newly identified mechanism is consistent with experimental kinetic data, the impact of mutating the corresponding lysine in mouse Dicer, and the active site architectures and proposed mechanisms for other related nucleases. Directed by the enhanced understanding of wild-type Dicer function, MD simulations subsequently show that six known DICER1 syndrome-causing mutants likely impede catalysis by inducing unique active site disruptions that inhibit Mg²⁺-ion coordination to the substrate. By furthering our knowledge of the structure and catalytic mechanism of wild-type and mutant Dicer, this work unveils the molecular underpinnings of DICER1 syndrome and opens the door for the development of enhanced RNAi-based therapeutics and biotechnologies.</p>","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"47 18","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcc.70446","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148381312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quadruple Bonding of Alkaline Earth Atoms in AeCLi4 (Ae = Be − Ba) Complexes","authors":"Yahui Li,&nbsp;Chengxiang Ding,&nbsp;Sudip Pan,&nbsp;Gernot Frenking","doi":"10.1002/jcc.70449","DOIUrl":"10.1002/jcc.70449","url":null,"abstract":"<p>The results of quantum chemical calculations of the complexes AeCLi₄ (Ae = Be − Ba) are reported at the BP86-D3(BJ)/def2-QZVPP and CCSD(T)/def2-QZVPP level. The calculated equilibrium geometries with Ae = Be, Mg have a trigonal bipyramidal geometry (<i>C</i>_<i>3v</i> symmetry) as the energetically lowest-lying form. A slightly higher-lying isomer has a square pyramidal geometry (<i>C</i>_4<i>v</i> symmetry), which is only &lt; 1 kcal/mol less stable than the <i>C</i>_3<i>v</i> form. In contrast, only the square pyramidal structure is an energy minimum of the heavier homologues with Ae = Ca, Sr, Ba. The calculated bond dissociation energies of the Ae-CLi₄ bond are very high. The strongest bond is computed for the Be-CLi₄ bond (<i>D</i>_e = 82.9 kcal/mol at CCSD(T)/def2-QZVPP). The weakest bond is calculated for the Mg-CLi₄ bond (<i>D</i>_e = 40.6 kcal/mol). The heavier homologues have values between <i>D</i>_e = 63.1 kcal/mol (Sr-CLi₄) and <i>D</i>_e = 72.0 kcal/mol (Ba-CLi₄). Inspection of the occupied valence orbitals and the AdNDP results suggests that there are four Ae-CLi₄ bonds in the complexes. This is supported by the EDA-NOCV analysis, which reveals that there is a dominant Ae → CLi₄ σ-donation, which is enhanced by weaker Ae ← CLi₄ σ-backdonation and degenerate Ae ← CLi₄ π-backdonation. The best signature of the chemical bonds is Ae  CLi₄. The lighter atoms, Be, Mg, use their (n)s and (n)p AOs for the covalent bonds, whereas the heavier atoms, Ca, Sr. Ba, employ their (n)s and (n-1)d AOs for the covalent interactions. The NBO method does not provide a reasonable account of the covalent bonds, because it does not consider the (n)p and (n-1)d AOs of Ae atoms as genuine valence orbitals.</p>","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"47 18","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcc.70449","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148379822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electric-Field Effects on Structure and Conductance in a Cytochrome b562 Junction","authors":"Gowtham Nirmal Jonnalagadda,&nbsp;Zdenek Futera","doi":"10.1002/jcc.70455","DOIUrl":"10.1002/jcc.70455","url":null,"abstract":"<div>\u0000 \u0000 <p>Electric fields present under experimental bias can significantly affect the structure and conductance of biomolecular junctions, especially in large, charged proteins. Here, we develop a multiscale computational framework to study these effects in an extended junction based on the redox protein cytochrome b₅₆₂, a system too large for straightforward application of non-equilibrium Green's function (NEGF) methods, which are typically used for molecular-junction calculations. The approach combines non-equilibrium classical molecular dynamics (MD), density functional theory (DFT) calculations with external electric fields, and approximate transport calculations based on the projection operator diabatization (POD) method. This enables us to disentangle electronic polarization from field-induced structural changes and to assess their combined influence on tunneling conductance in vacuum and aqueous solution. We show that electric fields induce asymmetries in conductance and current responses with respect to applied bias. The structural field response is partly compensated by electronic polarization in both vacuum and aqueous solution. Whereas the protein model is neutral in vacuum and the field response is dominated by dipole interactions, charged (de)protonated groups in solution are screened by polar water molecules and ions. Therefore, the total field effects are relatively weak and represent only a small perturbation to the conductance.</p>\u0000 </div>","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"47 18","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148372567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PES2MP: A Python Application for Automating Collisional Dynamics of Linear Rigid-Rotors","authors":"Apoorv Kushwaha,&nbsp;Pooja Chahal,&nbsp;Habit Tatin,&nbsp;T. J. Dhilip Kumar","doi":"10.1002/jcc.70439","DOIUrl":"https://doi.org/10.1002/jcc.70439","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 &lt;p&gt;The paper introduces a modular Python-based program with a graphical user interface (GUI) to automate collisional dynamics of rigid-rotors in cold and ultracold environments. The program streamlines the construction of ab initio potential energy surfaces (PES), with optional neural network (NN) augmentation, thereby reducing computational costs. The multipole expansion module generates radial terms for &lt;span&gt;Molscat&lt;/span&gt; to compute inelastic cross-sections and state-to-state rate coefficients. These rate coefficients, especially with hydrogen and helium, are crucial for determining column densities and modeling the abundances of species in the interstellar medium. In the paper, the rate coefficients of &lt;span&gt;&lt;/span&gt;&lt;math&gt;\u0000 &lt;semantics&gt;\u0000 &lt;mrow&gt;\u0000 &lt;msub&gt;\u0000 &lt;mrow&gt;\u0000 &lt;mtext&gt;C&lt;/mtext&gt;\u0000 &lt;/mrow&gt;\u0000 &lt;mrow&gt;\u0000 &lt;mn&gt;2&lt;/mn&gt;\u0000 &lt;/mrow&gt;\u0000 &lt;/msub&gt;\u0000 &lt;/mrow&gt;\u0000 &lt;annotation&gt;$$ {mathrm{C}}_2 $$&lt;/annotation&gt;\u0000 &lt;/semantics&gt;&lt;/math&gt;-He/&lt;span&gt;&lt;/span&gt;&lt;math&gt;\u0000 &lt;semantics&gt;\u0000 &lt;mrow&gt;\u0000 &lt;msub&gt;\u0000 &lt;mrow&gt;\u0000 &lt;mtext&gt;H&lt;/mtext&gt;\u0000 &lt;/mrow&gt;\u0000 &lt;mrow&gt;\u0000 &lt;mn&gt;2&lt;/mn&gt;\u0000 &lt;/mrow&gt;\u0000 &lt;/msub&gt;\u0000 &lt;/mrow&gt;\u0000 &lt;annotation&gt;$$ {mathrm{H}}_2 $$&lt;/annotation&gt;\u0000 &lt;/semantics&gt;&lt;/math&gt; are calculated for the first 11 rotational states to evaluate the accuracy of the ab initio and NN methods. Finally, the rate propensities for &lt;span&gt;&lt;/span&gt;&lt;math&gt;\u0000 &lt;semantics&gt;\u0000 &lt;mrow&gt;\u0000 &lt;msub&gt;\u0000 &lt;mrow&gt;\u0000 &lt;mtext&gt;C&lt;/mtext&gt;\u0000 &lt;/mrow&gt;\u0000 &lt;mrow&gt;\u0000 &lt;mtext&gt;n&lt;/mtext&gt;\u0000 &lt;/mrow&gt;\u0000 &lt;/msub&gt;\u0000 &lt;/mrow&gt;\u0000 &lt;annotation&gt;$$ {mathrm{C}}_{mathrm{n}} $$&lt;/annotation&gt;\u0000 &lt;/semantics&gt;&lt;/math&gt;, &lt;span&gt;&lt;/span&gt;&lt;math&gt;\u0000 &lt;semantics&gt;\u0000 &lt;mrow&gt;\u0000 &lt;msub&gt;\u0000 &lt;mrow&gt;\u0000 &lt;mtext&gt;HC&lt;/mtext&gt;\u0000 &lt;/mrow&gt;\u0000 &lt;mrow&gt;\u0000 &lt;mtext&gt;n&lt;/mtext&gt;\u0000 &lt;/mrow&gt;\u0000 &lt;/msub&gt;\u0000 &lt;/mrow&gt;\u0000 &lt;annotation&gt;$$ {mathrm{HC}}_{mathrm{n}} $$&lt;/annotation&gt;\u0000 &lt;/semantics&gt;&lt;/math&gt;, &lt;span&gt;&lt;/span&gt;&lt;math&gt;\u0000 &lt;semantics&gt;\u0000 &lt;mrow&gt;\u0000 &lt;msubsup&gt;\u0000 &lt;mrow&gt;\u0000 &lt;mtext&gt;HC&lt;/mtext&gt;\u0000 &lt;/mrow&gt;\u0000 &lt;mrow&gt;\u0000 &lt;mtext&gt;n&lt;/mtext&gt;\u0000 &lt;/mrow&gt;\u0000 &lt;mrow&gt;\u0000 &lt;mo&gt;−&lt;/mo&gt;\u0000 &lt;/mrow&gt;\u0000 ","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"47 18","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148358072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Projection-Modified Direct Inversion in the Iterative Subspace: A Memory-Efficient Convergence Method for the Extended Molecular Ornstein–Zernike Theory","authors":"Yusei Matsui,&nbsp;Norio Yoshida","doi":"10.1002/jcc.70450","DOIUrl":"10.1002/jcc.70450","url":null,"abstract":"<div>\u0000 \u0000 <p>The extended molecular Ornstein–Zernike (XMOZ) theory which is based on statistical mechanics explicitly incorporates solvent orientational degrees of freedom through expansion in generalized spherical harmonics, enabling detailed analysis of anisotropic solvation environments. This study develops a new convergence method, termed the projection-modified direct inversion in the iterative subspace (PMDIIS) method. This approach applies the MDIIS algorithm only to selected components of the generalized spherical harmonic expansion, while the remaining components are updated directly from the iterative solution. Applications of PMDIIS-accelerated XMOZ calculations to aqueous solutions of glycine, Trp-cage, and hen egg-white lysozyme show that PMDIIS achieves convergence performance comparable to that of the conventional MDIIS method while markedly reducing memory usage. Solvent distribution functions derived from the XMOZ theory not only reproduce hydrogen-bonding structures but also reveal internal water molecules in protein cavities. These findings reveal that PMDIIS provides a practical and memory-efficient solver for XMOZ calculations.</p>\u0000 </div>","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"47 18","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148372559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantum Chemistry Study of Luminescence Quenching in the Eu3+@UiO-67 Sensor Induced by Ag+ Ions","authors":"Yoslainy Echevarria-Valdés,&nbsp;Yoan Hidalgo-Rosa,&nbsp;Eduardo Schott,&nbsp;Mario Saavedra-Torres,&nbsp;Dayán Páez-Hernández,&nbsp;Ximena Zarate","doi":"10.1002/jcc.70452","DOIUrl":"10.1002/jcc.70452","url":null,"abstract":"<div>\u0000 \u0000 <p>The Eu³⁺/Ag⁺@UiO-67 system consists of a Zr₆O₄(OH)₄-based UiO-67 metal–organic framework (MOF) functionalized with 2,2′-bipyridine-5,5′-dicarboxylic acid (H₂bpydc) linkers, where Eu³⁺ and Ag⁺ ions are incorporated via post-synthetic metal–N coordination. The presence of both lanthanide and transition metal ions creates a co-doped architecture in which the photophysical properties are strongly influenced by metal–ligand interactions. This work focuses on elucidating, using theoretical tools, the luminescence-quenching mechanism induced by Ag⁺ co-doping in the Eu³⁺@UiO-67 system. To achieve this objective, a comprehensive theoretical protocol combining periodic DFT-based density of states (DOS) studies, TD-DFT excited-state analysis, and multiconfigurational CASSCF/NEVPT2 calculations was employed. Special attention was devoted to evaluating the efficiency of intersystem crossing (ISC) in the linker and the energy transfer (ET) pathways required to populate the emissive excited states of Eu³⁺. The results reveal that Ag⁺ insertion disrupts the linker to lanthanide ET process by promoting electronic states localized on the Ag⁺ centers, thereby reducing the effective T₁ population and sensitization efficiency. DOS analysis further supports this mechanism, showing orbital overlap between linker and Ag⁺ states near the conduction band edge, consistent with the experimentally observed luminescence “<i>turn-off</i>” effect induced by the co-dopant.</p>\u0000 </div>","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"47 18","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148372558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Anionic States of Ubiquinone Characterized by Second-Order Approximate Coupled-Cluster Theory","authors":"Mauro Gascón,&nbsp;Robin E. Moorby,&nbsp;Thomas-C. Jagau","doi":"10.1002/jcc.70406","DOIUrl":"10.1002/jcc.70406","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 &lt;p&gt;The reduction of ubiquinone is a critical step in cellular respiration thanks to its electron-accepting properties. Ubiquinone supports two distinct anionic states: a valence state and a non-valence, dipole-bound state. Dipole-bound states, where an excess electron is weakly bound by the molecular dipole, are of significant interest as potential doorway states for electron transfer processes. In this work, we employ the electron-attachment variant of the second-order approximate coupled-cluster (CC2) method to investigate the anionic states of ubiquinone analogues, Q&lt;sub&gt;0&lt;/sub&gt; and Q&lt;sub&gt;1&lt;/sub&gt;. We characterize the conformational energy, molecular dipole, and dipole-bound state and valence state binding energies as a function of the two relevant coordinates of the system, which are the dihedral angles between the methoxy groups and the benzene ring. We find that the vertical electron affinity of the valence state varies by &lt;span&gt;&lt;/span&gt;&lt;math&gt;\u0000 &lt;semantics&gt;\u0000 &lt;mrow&gt;\u0000 &lt;mo&gt;∼&lt;/mo&gt;\u0000 &lt;mn&gt;0&lt;/mn&gt;\u0000 &lt;mo&gt;.&lt;/mo&gt;\u0000 &lt;mn&gt;2&lt;/mn&gt;\u0000 &lt;mspace&gt;&lt;/mspace&gt;\u0000 &lt;mtext&gt;eV&lt;/mtext&gt;\u0000 &lt;/mrow&gt;\u0000 &lt;annotation&gt;$$ sim 0.2kern0.3em mathrm{eV} $$&lt;/annotation&gt;\u0000 &lt;/semantics&gt;&lt;/math&gt; over thermally accessible regions, whereas the dipole-bound state appears discontinuously, governed by both dipole magnitude and orientation. Addition of a single isoprenoid unit to Q&lt;sub&gt;0&lt;/sub&gt;, resulting in Q&lt;sub&gt;1&lt;/sub&gt;, modestly reshapes the regions that support the dipole-bound state, but leaves the valence state surface essentially unchanged. Cluster scans with small molecules (&lt;span&gt;&lt;/span&gt;&lt;math&gt;\u0000 &lt;semantics&gt;\u0000 &lt;mrow&gt;\u0000 &lt;msub&gt;\u0000 &lt;mrow&gt;\u0000 &lt;mtext&gt;H&lt;/mtext&gt;\u0000 &lt;/mrow&gt;\u0000 &lt;mrow&gt;\u0000 &lt;mn&gt;2&lt;/mn&gt;\u0000 &lt;/mrow&gt;\u0000 &lt;/msub&gt;\u0000 &lt;mtext&gt;O&lt;/mtext&gt;\u0000 &lt;/mrow&gt;\u0000 &lt;annotation&gt;$$ {mathrm{H}}_2mathrm{O} $$&lt;/annotation&gt;\u0000 &lt;/semantics&gt;&lt;/math&gt;, HF, &lt;span&gt;&lt;/span&gt;&lt;math&gt;\u0000 &lt;semantics&gt;\u0000 &lt;mrow&gt;\u0000 &lt;msub&gt;\u0000 &lt;mrow&gt;\u0000 &lt;mtext&gt;NH&lt;/mtext&gt;\u0000 &lt;/mrow&gt;\u0000 &lt;mrow&gt;\u0000 &lt;mn&gt;3&lt;/mn&gt;\u0000 &lt;/mrow&gt;\u0000 &lt;/msub&gt;\u0000 &lt;/mrow&gt;\u0000 &lt;annotation&gt;$$ {mathrm{NH}}_3 $$&lt;/annotation&gt;\u0000 &lt;/semantics&gt;&lt;/math&gt;, and &lt;span&gt;&lt;/span&gt;&lt;math&gt;\u0000 &lt;semantics&gt;\u0000 &lt;mrow&gt;\u0000 &lt;msub&gt;\u0000 &lt;mrow&gt;\u0000 &lt;mtext&gt;CH&lt;/mtext&gt;\u0000 &lt;/mrow&gt;\u0000 &lt;mrow&gt;\u0000 &lt;mn&gt;4&lt;/mn&gt;\u0000 &lt;/mrow&gt;\u0000 &lt;/msub&gt;\u0000 &lt;/mrow&gt;\u0000 &lt;annotation&gt;$$ {","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"47 17","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148314945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hydrogen Bond Energy Estimation in Large Molecular Clusters via the Method of Synergistic Cyclic Cooperativity: A Software Update H-BEE 2.0","authors":"Ayush Shivhare,&nbsp;Mini Bharati Ahirwar,&nbsp;Subodh S. Khire,&nbsp;Shridhar R. Gadre,&nbsp;Milind M. Deshmukh","doi":"10.1002/jcc.70443","DOIUrl":"10.1002/jcc.70443","url":null,"abstract":"<div>\u0000 \u0000 <p>Our earlier developed software utility, H-BEE, for estimating the energies of individual hydrogen bonds (HB) in molecular clusters was implemented with three methods. These methods are: the molecular tailoring approach based (MTA-based) one, the first spherical shell (SS1), and the Fragments-in-Fragments. These methods work quite well but are still time-consuming and have certain shortcomings. Herein, our recently proposed method of synergistic cyclic cooperativity (SCC) is implemented as an update (called H-BEE 2.0) to H-BEE. The three-dimensional (3D) molecular cluster is usually made up of small cyclic structures which result from the interconnected network of HBs. Within the SCC method, the energy of a referenced HB is estimated as the sum of the cooperativity contributions (CCs) of these small cyclic structures and its energy in an isolated dimeric species. The SCC is an effective and swift method. The H-BEE 2.0 identifies all possible cyclic structures in an automatic manner and evaluates the CCs of these cycles. The H-BEE 2.0 utility has been extensively tested on a variety of molecular clusters and the results are compared with the earlier implemented methods. It also brings out the finer aspects of the strength of HBs in terms of the nature of cooperativity of small cyclic networks.</p>\u0000 </div>","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"47 17","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148305027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights to Orientation Dependence of Molecular Conduction Modeled by High-Level Quantum Embedding","authors":"Dávid P. Jelenfi,&nbsp;Abdalghani H. S. Daaoub,&nbsp;Attila Tajti,&nbsp;Péter G. Szalay","doi":"10.1002/jcc.70442","DOIUrl":"10.1002/jcc.70442","url":null,"abstract":"<p>This work investigates how molecular orientation and electrode–molecule interactions influence conductance variations in single-molecule junctions using recently introduced methods that utilize quantum embedding within the NEGF framework. By generating conductance histograms from transmission functions for two experimentally studied systems, we assess the ability of several embedding schemes and conventional DFT approaches to reproduce experimentally observed distributions. The results show that while the wavefunction-in-DFT, SOS-ADC(2)-in-PBE method provides the most balanced description of both mean conductance and histogram width, no method fully captures the behavior of the more rigid dithienophosphole system, likely due to limitations of the underlying structural sampling. These findings highlight the importance of realistic configurational sampling and demonstrate that conductance histograms offer a sensitive benchmark for evaluating theoretical transport methodologies.</p>","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"47 17","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcc.70442","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148300288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Molecular “Thermometer” for Measuring Effective Non-Local Exchange","authors":"Stefan Grimme,&nbsp;Marcel Müller,&nbsp;Thomas Froitzheim,&nbsp;Andreas Hansen","doi":"10.1002/jcc.70436","DOIUrl":"10.1002/jcc.70436","url":null,"abstract":"<p>Non-local exchange (NLX) is a key ingredient for accurate density functional calculations, but its effective strength is often hard to quantify beyond simple global hybrids. To this end, we introduce a molecular probe based on the isomerization of hexaethynylbenzene to <i>carbo</i>-benzene, a reaction with exceptional sensitivity to exchange effects. Using the isomerization energy, we define a simple relative measure, <span></span><math>\u0000 <semantics>\u0000 <mrow>\u0000 <msub>\u0000 <mi>t</mi>\u0000 <mi>X</mi>\u0000 </msub>\u0000 </mrow>\u0000 <annotation>$$ {t}_{mathrm{X}} $$</annotation>\u0000 </semantics></math>, that gauges the effective NLX of a method on a scale ranging from 0 for the local density approximation to 100 for Hartree-Fock. Across a broad set of density functional approximations, <span></span><math>\u0000 <semantics>\u0000 <mrow>\u0000 <msub>\u0000 <mi>t</mi>\u0000 <mi>X</mi>\u0000 </msub>\u0000 </mrow>\u0000 <annotation>$$ {t}_{mathrm{X}} $$</annotation>\u0000 </semantics></math> closely tracks the formal Hartree-Fock exchange content of global hybrids, while revealing that most common GGAs, meta-GGAs, and global hybrids still provide too little effective exchange. Several range-separated hybrid, double hybrid, and some local hybrid functionals perform much better and closely approach the near-basis-set-limit coupled-cluster reference value of <span></span><math>\u0000 <semantics>\u0000 <mrow>\u0000 <msub>\u0000 <mi>t</mi>\u0000 <mi>X</mi>\u0000 </msub>\u0000 <mo>=</mo>\u0000 <mn>60</mn>\u0000 </mrow>\u0000 <annotation>$$ {t}_{mathrm{X}}=60 $$</annotation>\u0000 </semantics></math>. The <span></span><math>\u0000 <semantics>\u0000 <mrow>\u0000 <msub>\u0000 <mi>t</mi>\u0000 <mi>X</mi>\u0000 </msub>\u0000 </mrow>\u0000 <annotation>$$ {t}_{mathrm{X}} $$</annotation>\u0000 </semantics></math> values of various semiempirical quantum mechanical and machine-learned interatomic potential methods indicate that they empirically account for NLX effects to a varying degree. Thus, the proposed reaction serves as a compact thermochemical benchmark for assessing and developing methods that aim to reliably describe NLX.</p>","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"47 17","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcc.70436","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148300311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}