Journal of Computational Chemistry最新文献

{"title":"goChem: A Composable Library for Multi-Scale Computational Chemistry Data Analysis","authors":"Moisés Domínguez,&nbsp;Verónica A. Jiménez,&nbsp;Gökcen Savasci,&nbsp;Rocío Araya-Osorio,&nbsp;Janne Pesonen,&nbsp;Raúl Mera-Adasme","doi":"10.1002/jcc.70004","DOIUrl":"10.1002/jcc.70004","url":null,"abstract":"<div>\u0000 \u0000 <p>Data analysis is a major task for Computational Chemists. The diversity of modeling tools currently available in Computational Chemistry requires the development of flexible analysis tools that can adapt to different systems and output formats. As a contribution to this need, we report the implementation of goChem, a versatile open-source library for multiscale analysis of computational chemistry data. The library, written in and for the Go programming language, allows for easy integration of different levels of theory, in an easy-to-use API, allowing the development of both one-use and complex analysis programs in Go. We describe the library and detail some selected applications that illustrate the capabilities and potential of this tool. The library is available at http://gochem.org.</p>\u0000 </div>","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"46 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142961534","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":"COX-2 Inhibitor Prediction With KNIME: A Codeless Automated Machine Learning-Based Virtual Screening Workflow","authors":"Powsali Ghosh,&nbsp;Ashok Kumar,&nbsp;Sushil Kumar Singh","doi":"10.1002/jcc.70030","DOIUrl":"10.1002/jcc.70030","url":null,"abstract":"<div>\u0000 \u0000 <p>Cyclooxygenase-2 (COX-2) is an enzyme that plays a crucial role in inflammation by converting arachidonic acid into prostaglandins. The overexpression of enzyme is associated with conditions such as cancer, arthritis, and Alzheimer's disease (AD), where it contributes to neuroinflammation. In silico virtual screening is pivotal in early-stage drug discovery; however, the absence of coding or machine learning expertise can impede the development of reliable computational models capable of accurately predicting inhibitor compounds based on their chemical structure. In this study, we developed an automated KNIME workflow for predicting the COX-2 inhibitory potential of novel molecules by building a multi-level ensemble model constructed with five machine learning algorithms (i.e., Logistic Regression, K-Nearest Neighbors, Decision Tree, Random Forest, and Extreme Gradient Boosting) and various molecular and fingerprint descriptors (i.e., AtomPair, Avalon, MACCS, Morgan, RDKit, and Pattern). Post-applicability domain filtering, the final majority voting-based ensemble model achieved 90.0% balanced accuracy, 87.7% precision, and 86.4% recall on the external validation set. The freely accessible workflow empowers users to swiftly and effortlessly predict COX-2 inhibitors, eliminating the need for any prior knowledge in machine learning, coding, or statistical modeling, significantly broadening its accessibility. While beginners can seamlessly use the tool as is, experienced KNIME users can leverage it as a foundation to build advanced workflows, driving further research and innovation.</p>\u0000 </div>","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"46 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142961946","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":"Photodissociation of \u0000 \u0000 \u0000 \u0000 \u0000 Cr(CO)\u0000 \u0000 \u0000 4\u0000 \u0000 \u0000 bpy\u0000 \u0000 $$ mathrm{Cr}{left(mathrm{CO}right)}_4mathrm{bpy} $$\u0000 : A Non-Adiabatic Dynamics Investigation","authors":"Bartosz Ciborowski,&nbsp;Morgane Vacher","doi":"10.1002/jcc.70021","DOIUrl":"10.1002/jcc.70021","url":null,"abstract":"<p>Carbonyl complexes of <span></span><math>\u0000 <semantics>\u0000 <mrow>\u0000 <msup>\u0000 <mrow>\u0000 <mi>d</mi>\u0000 </mrow>\u0000 <mrow>\u0000 <mn>6</mn>\u0000 </mrow>\u0000 </msup>\u0000 </mrow>\u0000 <annotation>$$ {d}^6 $$</annotation>\u0000 </semantics></math> metals with an α-diimine ligand exhibit both emission and ligand-selective photodissociation from MLCT states. Studying this photodissociative mechanism is challenging for experimental approaches due to an ultrafast femtosecond timescale and spectral overlap of multiple photoproducts. The photochemistry of a prototypical system <span></span><math>\u0000 <semantics>\u0000 <mrow>\u0000 <msub>\u0000 <mrow>\u0000 <mtext>Cr(CO)</mtext>\u0000 </mrow>\u0000 <mrow>\u0000 <mn>4</mn>\u0000 </mrow>\u0000 </msub>\u0000 <mtext>bpy</mtext>\u0000 </mrow>\u0000 <annotation>$$ mathrm{Cr}{left(mathrm{CO}right)}_4mathrm{bpy} $$</annotation>\u0000 </semantics></math> is investigated with non-adiabatic dynamic simulations. Obtained 86 fs lifetime of the bright <span></span><math>\u0000 <semantics>\u0000 <mrow>\u0000 <msub>\u0000 <mrow>\u0000 <mi>S</mi>\u0000 </mrow>\u0000 <mrow>\u0000 <mn>3</mn>\u0000 </mrow>\u0000 </msub>\u0000 </mrow>\u0000 <annotation>$$ {S}_3 $$</annotation>\u0000 </semantics></math> state and 13% quantum yield are in good agreement with experimental data. The present simulations suggest a ballistic mechanism of photodissociation, which is irrespective of the occupied electronic state. This is in contrast to the previously established mechanism of competitive intersystem crossing and dissociation. Selectivity of axial photodissociation is shown to be caused by the absence of an avoided crossing in the equatorial direction.</p>","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"46 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcc.70021","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142961947","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":"From Antipsychotic to Neuroprotective: Computational Repurposing of Fluspirilene as a Potential PDE5 Inhibitor for Alzheimer's Disease","authors":"Kunal Bhattacharya,&nbsp;Atanu Bhattacharjee,&nbsp;Manodeep Chakraborty,&nbsp;Dibyajyoti Das,&nbsp;Keshav Raj Paudel","doi":"10.1002/jcc.70029","DOIUrl":"10.1002/jcc.70029","url":null,"abstract":"<div>\u0000 \u0000 <p>Phosphodiesterase 5 (PDE5) inhibitors have shown great potential in treating Alzheimer's disease by improving memory and cognitive function. In this study, we evaluated fluspirilene, a drug commonly used to treat schizophrenia, as a potential PDE5 inhibitor using computational methods. Molecular docking revealed that fluspirilene binds strongly to PDE5, supported by hydrophobic and aromatic interactions. Molecular dynamics simulations confirmed that the fluspirilene–PDE5 complex is stable and maintains its structural integrity over time. Binding energy calculations further highlighted favorable interactions, indicating that the drug forms a strong and stable bond with PDE5. Additional analyses, including studies of protein dynamics and energy landscape mapping, revealed how the drug interacts dynamically with PDE5, adapting to different conformations and maintaining stability. These findings suggest that fluspirilene may modulate PDE5 activity, potentially offering therapeutic benefits for Alzheimer's disease. This study provides strong evidence for repurposing fluspirilene as a treatment for Alzheimer's and lays the foundation for further experimental and clinical investigations.</p>\u0000 </div>","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"46 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142961951","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":"Exploring Mechanism and Kinetics of 1,4-Dioxane Oxidative Degradation by OH Radical: A Computational Quantum Chemistry Investigation","authors":"Gustavo Gomes de Sousa,&nbsp;João B. L. Martins,&nbsp;José Roberto dos Santos Politi","doi":"10.1002/jcc.70018","DOIUrl":"10.1002/jcc.70018","url":null,"abstract":"<div>\u0000 \u0000 <p>This study aims to shed light on the mechanism and kinetics of 1,4-dioxane degradation by hydroxyl radical (OH) across various solvation conditions to evaluate electronic and structural properties at the MP2/aug-cc-pVTZ level. Transition states (TS) structures determined in the gas phase and SMD solvation model reveal similar hydrogen abstraction patterns. In contrast, the explicit solvation model (ES) introduces significant changes, suggesting a kinetic preference for axial pathways. The reaction rate constants, employing Deformed Transition State Theory (d-TST), are consistently higher for axial abstraction. The preference for axial hydrogen abstraction, solvation effects on transition states, and temperature-dependent rate constants are highlighted. Furthermore, the identification of carbon–carbon orbital distortion suggests potential bond breakage. This research provides valuable insights into the reaction between 1,4-dioxane and OH radical across different solvation models and enhances the understanding of the advanced oxidative process.</p>\u0000 </div>","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"46 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142961954","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":"Extending the MST Model to Large Biomolecular Systems: Parametrization of the ddCOSMO-MST Continuum Solvation Model","authors":"R. D. Cunha,&nbsp;S. Romero-Téllez,&nbsp;F. Lipparini,&nbsp;F. J. Luque,&nbsp;C. Curutchet","doi":"10.1002/jcc.70027","DOIUrl":"10.1002/jcc.70027","url":null,"abstract":"<div>\u0000 \u0000 <p>Continuum solvation models such as the polarizable continuum model and the conductor-like screening model are widely used in quantum chemistry, but their application to large biosystems is hampered by their computational cost. Here, we report the parametrization of the Miertus–Scrocco–Tomasi (MST) model for the prediction of hydration free energies of neutral and ionic molecules based on the domain decomposition formulation of COSMO (ddCOSMO), which allows a drastic reduction of the computational cost by several orders of magnitude. We also introduce several novelties in MST, like a new definition of atom types based on hybridization and an automatic setup of the cavity for charged regions. The model is parametrized at the B3LYP/6-31+G(d) and PM6 levels of theory and compared to the performance of IEFPCM/MST. Then, we demonstrate the robustness of the parametrization on the SAMPL2, SAMPL4, and C10 datasets. The ddCOSMO/MST models provide errors of ~0.8 and ~3.2 kcal/mol for neutrals and ions, respectively, showing a remarkable balanced and accurate description of cations and anions.</p>\u0000 </div>","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"46 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142961538","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":"Practical Machine Learning Strategies. I. Correcting the MMFF Molecular Mechanics Model to More Accurately Provide Conformational Energy Differences in Flexible Organic Molecules","authors":"Thomas Hehre,&nbsp;Philip E. Klunzinger,&nbsp;Bernard Deppmeier,&nbsp;William Ohlinger,&nbsp;Warren Hehre","doi":"10.1002/jcc.70016","DOIUrl":"10.1002/jcc.70016","url":null,"abstract":"<div>\u0000 \u0000 <p>A correction to the MMFF molecular mechanics model, based on a neural network trained to reproduce conformer energy differences obtained from ωB97X-V/6-311+G(2df,2p)[6-311G*]//MMFF calculations is described. It is supported for molecules containing H, C, N, O, F, S, Cl, and Br. The correction adds only slightly to the cost of MMFF, and the resulting corrected model is several orders of magnitude faster than ωB97X-V/6-311+G(2df,2p)[6-311G*]. It properly identifies the lowest energy conformer for 82% of the molecules in a test set of flexible organic molecules (3553 total conformers), compared with 38% for MMFF. While the corrected MMFF model cannot be expected to provide sufficiently accurate Boltzmann weights for use in spectra and property calculations on flexible molecules, it is able to reduce the number of “reasonable” conformers that need to be passed on to more rigorous computational models, that can.</p>\u0000 </div>","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"46 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142929674","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":"Thermodynamic Stability in Transition Metal-Hydrogen Dications: Potential Energy Curves, Spectroscopic Parameters, and Bonding for VH2+","authors":"João Gabriel Farias Romeu,&nbsp;Fernando R. Ornellas","doi":"10.1002/jcc.27530","DOIUrl":"10.1002/jcc.27530","url":null,"abstract":"<div>\u0000 \u0000 <p>Seventeen electronic states of the dication VH²⁺ were characterized by the SA-CASSCF/icMRCI methodology using very extended basis sets; 11 were described for the first time. Potential energy curves were constructed and the associated spectroscopic parameters evaluated. Triplet and quintet states correlating with the V²⁺ + H channel are thermodynamic stable. For states dissociating into the channel V⁺ + H⁺, avoided crossings at large distances give rise to thermodynamic metastability but do not affect the characterization of the bound region. Configuration state functions with the 3σ orbital /doubly occupied give rise to covalent contributions to the bonding; the major contribution, however, comes from the electrostatic charge-induced dipole interaction. This explains the shape and proximity of the potential energy curves beyond their equilibrium distances. Dipole moment functions and vibrationally averaged dipole moments quantify the polarity of the molecule. Spin–orbit couplings give rise to complex and dense regions of very close-lying Ω states.</p>\u0000 </div>","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"46 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142924529","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":"Appraisal of the Fragments-In-Fragments Method for the Energetics of Individual Hydrogen Bonds in Molecular Crystals","authors":"Bharti Dehariya,&nbsp;Mini Bharati Ahirwar,&nbsp;Ayush Shivhare,&nbsp;Milind M. Deshmukh","doi":"10.1002/jcc.70008","DOIUrl":"10.1002/jcc.70008","url":null,"abstract":"<div>\u0000 \u0000 <p>We report a direct application of the molecular tailoring approach-based (MTA-based) method to calculate the individual hydrogen bond (HB) energy in molecular crystal. For this purpose, molecular crystals of nitromalonamide (NMA) and salicylic acid (SA) were taken as test cases. Notably, doing a correlated computation using a large molecular crystal structure is difficult. Among 15 density functional theory functionals, the B3LYP provides accurate estimates of HB energies closed to the CCSD(T) ones using the 6–311 + G(d,p) basis set for all atoms. The direct application of the MTA-based method to these crystal structures is although straightforward. For instance, the calculated energy suggests that three intramolecular HBs in NMA crystal are of stronger strength (7.3–17.0 kcal/mol) than the intermolecular ones (2.7–4.0 kcal/mol). On the other hand, intermolecular HB in SA crystal is moderately stronger (9.9 kcal/mol) than intramolecular one (8.1 kcal/mol). However, these energy calculations by the MTA-based method are very expensive. For instance, the time needed to evaluate the energy of all seven HBs in NMA crystal (having molecules within maximum of 15 unit cells) is 122,681 min (~2.7 months). In view of this, we assessed our recently proposed linear-scaling Fragments-in-Fragments (<i>Frags-in-Frags</i>) method for estimating the single-point energies of parent molecular crystal and fragments of the MTA-based method. It has been found that the estimated HB energies by the <i>Frags-in-Frags</i> method are in excellent linear agreement with their MTA-based counterparts (R² = 0.9993). Furthermore, root mean square deviation is 0.12 kcal/mol. Mean and maximum absolute errors are 0.10 and 0.5 kcal/mol, respectively, and the standard deviation is 0.14 kcal/mol. Importantly, the <i>Frags-in-Frags</i> method is computationally efficient; it needs only 18,289 min (~12.7 days) for the estimation of energy of all HBs in NMA crystal and 3499 min (~2.4 days) for all HBs in SA crystal.</p>\u0000 </div>","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"46 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142925100","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":"A Closer Look at the FeS Heme Bonds in Azotobacter vinelandii Bacterioferritin: QM/MM and Local Mode Analysis","authors":"Marek Freindorf,&nbsp;Elfi Kraka","doi":"10.1002/jcc.70012","DOIUrl":"10.1002/jcc.70012","url":null,"abstract":"<p>Using the QM/MM methodology and a local mode analysis, we investigated a character and a strength of FeS bonds of heme groups in oxidized and reduced forms of Bacterioferritin from <i>Azotobacter vinelandii</i>. The strength of the FeS bonds was correlated with a bond length, an energy density at a bond critical point, and a charge difference of the F and S atoms. Changing the oxidation state from ferrous to ferric generally makes the FeS bonds weaker, longer, more covalent, and more polar. We also investigated the SFeS bond bending and found that the stronger FeS bond, generally makes the SFeS bond bending stiffer, which could play a key role in the balance between ferric and ferrous oxidation states and related biological activities.</p>","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"46 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcc.70012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142917200","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}