Journal of Computational Chemistry最新文献

{"title":"In Honor of Prof. Peter R. Schreiner","authors":"Gernot Frenking, Ralph Puchta, Michael Haley, Rik Tykwinski","doi":"10.1002/jcc.70457","DOIUrl":"10.1002/jcc.70457","url":null,"abstract":"","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"47 19","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148432932","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":"Exactly Factorized Molecular Kohn–Sham Density Functional Theory","authors":"Lucien Dupuy,&nbsp;Benjamin Lasorne,&nbsp;Emmanuel Fromager","doi":"10.1002/jcc.70459","DOIUrl":"10.1002/jcc.70459","url":null,"abstract":"<div>\u0000 \u0000 <p>Fromager and Lasorne [<i>Electron. Struct.</i> <b>6</b> 025002 (2024)] have recently derived an in-principle exact Kohn–Sham density functional theory (KS-DFT) of electrons and nuclei, where the nuclear density and the (so-called conditional) electronic density are mapped onto a fictitious electronically non-interacting KS molecule. In this work, we apply the exact factorization formalism to the molecular KS wavefunction, thus leading to disentangled (but coupled) marginal and conditional KS equations. We show that, while being equivalent to the original theory, these equations open new perspectives in the practical extension of regular (electronic) KS-DFT beyond the Born Oppenheimer approximation. The importance and treatment of correlations induced in this context by second-order geometrical derivatives is also discussed.</p>\u0000 </div>","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"47 19","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148428909","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":"Unraveling the Mechanism of Drug Binding to SARS-CoV-2 RNA Pseudoknot With Thermodynamics-Driven Machine Learning","authors":"Mariia Ivonina,&nbsp;Jakub Rydzewski","doi":"10.1002/jcc.70461","DOIUrl":"10.1002/jcc.70461","url":null,"abstract":"<div>\u0000 \u0000 <p>The pseudoknot secondary structure in SARS-CoV-2 RNA is essential for regulating protein synthesis through <span></span><math>\u0000 <semantics>\u0000 <mrow>\u0000 <mo>−</mo>\u0000 </mrow>\u0000 <annotation>$$ - $$</annotation>\u0000 </semantics></math>1 programmed ribosomal frameshifting (<span></span><math>\u0000 <semantics>\u0000 <mrow>\u0000 <mo>−</mo>\u0000 <mn>1</mn>\u0000 </mrow>\u0000 <annotation>$$ -1 $$</annotation>\u0000 </semantics></math> PRF), a mechanism that allows the virus to generate both structural and non-structural proteins from overlapping reading frames. This pseudoknot exhibits both threaded and unthreaded long-lived topologies. The influence of ligand binding on its folding is a process critical for the development of <span></span><math>\u0000 <semantics>\u0000 <mrow>\u0000 <mo>−</mo>\u0000 </mrow>\u0000 <annotation>$$ - $$</annotation>\u0000 </semantics></math>1 PRF small-molecule inhibitors. Understanding this process through unbiased molecular dynamics (MD) simulations can be facilitated by introducing collective variables (CVs) that capture the corresponding slowest dynamical modes. Here, we use spectral map (SM), a thermodynamics-driven machine learning technique, to learn such CVs directly from all-atom MD trajectories of the SARS-CoV-2 RNA pseudoknot in complex with the <span></span><math>\u0000 <semantics>\u0000 <mrow>\u0000 <mo>−</mo>\u0000 </mrow>\u0000 <annotation>$$ - $$</annotation>\u0000 </semantics></math>1 PRF inhibitor merafloxacin and its two structural analogs in neutral and ionized forms. Free-energy landscapes (FELs) derived from the learned CVs indicate that ligand-induced destabilization is topology-selective. In the threaded pseudoknot, the inhibitors destabilize the S2 stem, while in the unthreaded pseudoknot, destabilization occurs in the S1 and S3 stems. Furthermore, the extent to which each ligand reshapes the FEL matches experimentally reported antiviral potency, whereas the protonation state qualitatively alters dynamics within the same RNA topology. Overall, our results show how pseudoknot topology, ligand type, and protonation state collectively influence the slow conformational dynamics of viral RNA and establish physiological protonation as a critical factor for modeling RNA-targeted drug action.</p>\u0000 </div>","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"47 19","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148415214","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":"Lithium Surface Restructuring and Dendrite-Like Protrusion Formation in Li-S Electrolytes From Reactive Molecular Simulations With Machine-Learned Potentials","authors":"Mirella Fonda Maahury,&nbsp;Sabrina Chin-yun Shen,&nbsp;Kayvon Tabrizi,&nbsp;Sam Walton Norwood,&nbsp;Cedric Naravisnu Purwanto,&nbsp;Ganes Shukri,&nbsp;Hasan Al Rasyid,&nbsp;Aditya Wibawa Sakti","doi":"10.1002/jcc.70466","DOIUrl":"10.1002/jcc.70466","url":null,"abstract":"<div>\u0000 \u0000 <p>Lithium-metal anodes present remarkable theoretical capacity for advanced batteries. However, their practical application is hindered by interfacial instabilities and dendritic lithium morphologies, which undermine safety and longevity. This study utilizes machine-learned interatomic potentials to conduct molecular dynamics simulations of the interface between a lithium-metal anode and an electrolyte composed of elemental sulfur (<span></span><math>\u0000 <semantics>\u0000 <mrow>\u0000 <msub>\u0000 <mi>S</mi>\u0000 <mn>8</mn>\u0000 </msub>\u0000 </mrow>\u0000 <annotation>$$ {mathrm{S}}_8 $$</annotation>\u0000 </semantics></math>), propylene carbonate (PC), and lithium Otf (LiOTf). Because the employed neutral MLIP does not explicitly describe electrode potential, electron transfer, or charge-state evolution, the simulations are interpreted as reactive structural models of lithium redistribution, aggregation, and protrusion growth rather than as a complete electrochemical plating/stripping description. Within this scope, the simulations provide atomistic insight into early dendrite-like lithium protrusions across different electrolyte compositions. Species detection, connection-matrix analysis, maximum protrusion height, and local-order analysis are used as complementary structural descriptors of interfacial reorganization. Supporting benchmarks against DFT include RDF validation for the interface model and structural and reaction-energy comparisons for adsorption and reaction in modeled lithium clusters. These benchmarks indicate that the r2SCAN readout gives more consistent structural and energetic agreement for the present lithium surface chemistry, whereas the <span></span><math>\u0000 <semantics>\u0000 <mrow>\u0000 <mi>ω</mi>\u0000 </mrow>\u0000 <annotation>$$ omega $$</annotation>\u0000 </semantics></math> B97X readout is retained as a sensitivity test for readout dependence. The findings provide an atomic-level view of how <span></span><math>\u0000 <semantics>\u0000 <mrow>\u0000 <msub>\u0000 <mi>S</mi>\u0000 <mn>8</mn>\u0000 </msub>\u0000 </mrow>\u0000 <annotation>$$ {mathrm{S}}_8 $$</annotation>\u0000 </semantics></math>, PC, and <span></span><math>\u0000 <semantics>\u0000 <mrow>\u0000 <msup>\u0000 <mi>Otf</mi>\u0000 <mo>−</mo>\u0000 </msup>\u0000 </mrow>\u0000 <annotation>$$ {mathrm{Otf}}^{-} $$</annotation>\u0000 </semantics></math> correlate with lithium aggregation and morphology changes in S₈/PC/LiOtf electrolytes, while clarifying the present limits of pre-trained MLIPs for mechanistic electrochemical interpretation.</p>\u0000 </div>","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"47 19","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148415135","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 Chemical Smiler: CHEMICal Abstraction Leading to SMILEs of Reference","authors":"Davide Luciani,&nbsp;Anna Lombardo,&nbsp;Emilio Benfenati","doi":"10.1002/jcc.70463","DOIUrl":"10.1002/jcc.70463","url":null,"abstract":"<div>\u0000 \u0000 <p>Linear notations such as SMILES describe molecular structure and are essential for chemical analysis and comparison. Their usability depends primarily on how much effort has been made to ensure a one-to-one correspondence between encoding and structure. Overcoming syntactical differences between notations has generally overshadowed the user's interest in a preliminary selection of chemical properties to encode. The proposed system allows for the disregarding of properties considered noncritical in the detection of molecular differences, such as tautomerism and stereochemistry, while accounting for multiple neutralized chemical forms. To this end, the system effectively extends the hierarchical structure of the nonstandard InChI notation. Several examples will demonstrate the importance of abstracting irrelevant details depending on the type of application, along with the usefulness of other functions to recover as much initial chemical information as possible, resolve any ambiguities in the register numbers used as identifiers, and facilitate secondary analyses of the SMILES produced.</p>\u0000 </div>","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"47 19","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148408386","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":"OpenCafeMol With 3SPN.2 DNA Model: GPU Acceleration for Long-Time Coarse-Grained Chromatin Simulations","authors":"Masataka Yamauchi,&nbsp;Yutaka Murata,&nbsp;Toru Niina,&nbsp;Shoji Takada","doi":"10.1002/jcc.70460","DOIUrl":"10.1002/jcc.70460","url":null,"abstract":"<div>\u0000 \u0000 <p>There is a growing demand for molecular dynamics simulations to explore longer timescale behavior of giant protein-DNA complexes such as chromatin. To address this need, we extended OpenCafeMol, a GPU-accelerated residue-level coarse-grained molecular dynamics simulator originally developed for proteins and lipids, to support 3SPN.2 and 3SPN.2C DNA models. We also implemented a hydrogen-bond-type many-body potential to model DNA-protein interactions more accurately. To further improve computational efficiency, we introduced a localized scheme for calculating base-pairing and cross-stacking interactions. Benchmark tests show that OpenCafeMol on a single GPU achieves up to 200-fold speed-up for DNA-only systems and up to 100-fold speed-up for DNA-protein complexes compared to CPU-based simulations. To demonstrate the capability of our implementation for long-timescale biological processes, we simulated an archaeal SMC-ScpA complex undergoing DNA translocation via segment capture (a proposed mechanism for DNA loop extrusion) in the presence of a DNA-bound obstacle. We observed continuous captured-loop growth accompanied by obstacle bypass within the segment capture framework.</p>\u0000 </div>","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"47 19","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148403023","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":"Nuclear Quantum Effects on the Organic Bifurcation Reaction in Microsolvated Water Clusters: Ring-Polymer Molecular Dynamics Calculations Using an Explicit Solvation Model","authors":"Shoto Nakagawa,&nbsp;Hayato Matsubuchi,&nbsp;Haruki Ota,&nbsp;Toshiyuki Takayanagi,&nbsp;Tatsuhiro Murakami","doi":"10.1002/jcc.70458","DOIUrl":"10.1002/jcc.70458","url":null,"abstract":"<p>Solvent environments often reshape reaction mechanisms compared to those obtained in the gas phase or in nonpolar solvents. Recently, explicit solvation models—where individual solvent molecules are treated—have been increasingly employed in simulations of organic reactions to capture the dynamic influence of solvent motions. In aqueous systems, the incorporation of nuclear quantum effects (NQEs) is particularly crucial for accurately describing both structural and dynamical features. Here, we investigate the bifurcation reaction between 2-aminoacrolein and 1,3-butadiene in microsolvated (H₂O)_<i>n</i> clusters (<i>n</i> = 5, 15, 45) using ring-polymer molecular dynamics (RPMD), and compare the results with our previous classical molecular dynamics (classical MD) simulations. The branching fractions obtained from RPMD trajectories exhibit an increased tendency toward the minor (4 + 2) product pathway—equivalently, a lower fraction of the dominant (4 + 3) channel—compared with classical MD, owing to zero-point energy contributions distributed across all vibrational modes of the system. Moreover, RPMD reveals significantly accelerated proton-transfer events, indicating that nuclear quantum effects, including zero-point energy and proton delocalization, contribute substantially even at 300 K. These findings demonstrate that reliable prediction of aqueous branching behavior and proton-transfer kinetics requires both explicit solvation and rigorous inclusion of NQEs.</p>","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"47 19","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcc.70458","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148393615","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":"Reaction Enumeration Based on NBO-Informed Molecular Graphs","authors":"Javier E. Alfonso-Ramos,&nbsp;Thijs Stuyver","doi":"10.1002/jcc.70462","DOIUrl":"https://doi.org/10.1002/jcc.70462","url":null,"abstract":"<p>Enumeration of reaction products and pathways is essential for understanding chemical reactivity and for the rational design of new chemical technologies. Traditional graph-based enumeration methods represent molecules through atomic connectivity and simple valency rules, with bond breaking and formation encoded as edge modifications. However, this representation becomes ambiguous for many important classes of chemical systems, including transition-metal complexes, hypervalent compounds, and molecules with extensive resonance or delocalization. Here, we introduce a molecular graph representation constructed at the level of valence orbitals rather than atomic connectivity alone. When combined with quantum-mechanical natural bond orbital (NBO) analysis, the method automatically detects delocalized bonding motifs and adaptively increases reaction-step complexity when chemically warranted. This integration enables systematic and computationally efficient identification of chemically meaningful reaction pathways that lie beyond the practical scope of conventional graph-based approaches. We demonstrate the robustness of the method across challenging bonding environments, including organometallic catalytic cycles, pericyclic reactions in highly delocalized systems, main-group hypervalent chemistry, and multicomponent reaction networks.</p>","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"47 19","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcc.70462","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148394995","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":"Computational Analysis of the (4+3) Cycloaddition Reaction of a Sulfoximine-Stabilized Oxyallylic Cation With Furan","authors":"Mary J. Richardson,&nbsp;Kurt R. Brorsen,&nbsp;Michael Harmata","doi":"10.1002/jcc.70412","DOIUrl":"10.1002/jcc.70412","url":null,"abstract":"<div>\u0000 \u0000 <p>Herein, we report a DFT study of a 4+3 cycloaddition reaction involving a theoretically proposed oxyallylic cation stabilized by a chiral sulfoximine group. The growing importance of the sulfoximine functional group in chemistry cannot be overstated. Computed energy profiles indicate that the reaction is feasible, and geometric and topological analyses (QTAIM, ESP, and NCI) of all transition-states elucidate bonding and the non-covalent interactions stabilizing the favored pathway. The results reveal a strong preference for the <i>endo</i> pathway with modest diastereoselectivity.</p>\u0000 </div>","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"47 19","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148393764","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":"From SMILES Codes for Reactants and Products to Transition States With VeloxChem","authors":"Bastiaan van Hoorn,&nbsp;Patrick Norman,&nbsp;Mårten S. G. Ahlquist","doi":"10.1002/jcc.70454","DOIUrl":"10.1002/jcc.70454","url":null,"abstract":"<p>A force field interpolation method for generating initial guesses for transition state optimizations is presented. The user supplies reactants and products as SMILES strings (or <i>XYZ</i> coordinates), after which automatically constructed force fields are interpolated to approximate the potential energy surface (PES) along the reaction coordinate. The transition state guess is obtained by sampling along this approximate PES. Reliance on force fields ensures the method is transparent in its workings and computationally inexpensive. The workflow is implemented in VeloxChem, enabling Jupyter notebook execution with a few lines of Python code. An interactive widget makes visualization and inspection of results easy and intuitive, and a flexible Python API facilitates integration into complex automated workflows. The method is demonstrated on ten chemically diverse systems, including a transition-metal catalytic cycle. Benchmarking across 121 reactions resulted in convergence for 115 transition states, with an average cost of 107 gradient evaluations per reaction—comparable to more demanding double-ended methods.</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.70454","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148379825","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}