Journal of Computational Chemistry最新文献

{"title":"The Intricate Mechanism of Nitric Oxide Synthase","authors":"Per E. M. Siegbahn","doi":"10.1002/jcc.70448","DOIUrl":"10.1002/jcc.70448","url":null,"abstract":"<p>The biological formation of NO is performed by nitric oxide synthase. For the first half of the mechanism, a consensus understanding has been reached, but not for the second half. Several attempts to reach a mechanism in agreement with experimental observations have been reported, but without success. Therefore, another study of that half-reaction has been made here. The main difficulties have been to explain the observed non-stoichiometric action of the cofactor H₄B, and also why only one outside reduction from NADP is enough. A key new finding here is that the first step involves a protonation of the proximal cysteine of the heme. O₂ then binds to iron and forms O₂H with a proton from the NOH ligand of the substrate NHA. A long-range electron transfer from H₄B leads to the formation of the heme bound H₂O₂, which is followed by a dissociation of the O<span></span>O bond of H₂O₂. The last step studied here was a release of NO and a reverse electron transfer back to H₄B. The results are in very good agreement with experimental observations, which is in line with previous findings for other redox enzymes using the present methodology.</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.70448","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148305029","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":"AutoSTOP-RT-TDDFT: Adaptive and Selected Real-Time Time-Dependent Density Functional Theory for Simulation of X-Ray Absorptions","authors":"Linfeng Ye,&nbsp;Hao Wang,&nbsp;Yong Zhang,&nbsp;Wenjian Liu","doi":"10.1002/jcc.70447","DOIUrl":"10.1002/jcc.70447","url":null,"abstract":"<div>\u0000 \u0000 <p>It has recently been shown [J. Chem. Phys. 157, 074106 (2022)] that the propagator (P), step size (S) and total time (T) required by real-time time-dependent density functional theory (RT-TDDFT) simulation of X-ray absorptions (XAS) can be determined automatically (Auto) for whatever chemical systems described by whatever electronic Hamiltonians and basis sets, by making use only of the ground-state Kohn–Sham core orbital energies. The AutoPST algorithm is improved here in two aspects: (1) a universal bivariate linear relation is established for accurate predication of the time steps for both <span></span><math>\u0000 <semantics>\u0000 <mrow>\u0000 <mi>K</mi>\u0000 </mrow>\u0000 <annotation>$$ K $$</annotation>\u0000 </semantics></math>- and <span></span><math>\u0000 <semantics>\u0000 <mrow>\u0000 <mi>L</mi>\u0000 </mrow>\u0000 <annotation>$$ L $$</annotation>\u0000 </semantics></math>-edge XAS of any desired spectral accuracy; (2) an automated orbital selection scheme is introduced to pick up only those “active” core and virtual canonical molecular orbitals (CMO), thereby extending AutoPST to AutoSTOP. Such orbital selection is particularly necessary when an uncontracted basis set is used, which generates many high-lying CMOs that have no contributions to near-edge XAS but render the time step exceedingly small. The ratio of the number of active CMOs over the total number of CMOs decreases quickly as the increase of molecular size, thereby ensuring computational efficiency. It is also shown that both singlet and triplet core excited states of a closed-shell system can be obtained by RT-TDDFT with a weak spin-dependent external field. Spin-orbit couplings between the so-obtained singlet and triplet states can then readily be calculated to obtain the <span></span><math>\u0000 <semantics>\u0000 <mrow>\u0000 <msub>\u0000 <mrow>\u0000 <mi>L</mi>\u0000 </mrow>\u0000 <mrow>\u0000 <mn>2</mn>\u0000 </mrow>\u0000 </msub>\u0000 </mrow>\u0000 <annotation>$$ {L}_2 $$</annotation>\u0000 </semantics></math> and <span></span><math>\u0000 <semantics>\u0000 <mrow>\u0000 <msub>\u0000 <mrow>\u0000 <mi>L</mi>\u0000 </mrow>\u0000 <mrow>\u0000 <mn>3</mn>\u0000 </mrow>\u0000 </msub>\u0000 </mrow>\u0000 <annotation>$$ {L}_3 $$</annotation>\u0000 </semantics></math> spectra. Finally, the linearized variant of RT-TDDFT is briefly discussed.</p>\u0000 </div>","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"47 17","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148289670","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":"PrimaDORAC: An improved Web Interface for Rapid GAFF2 Parameter Assignment with ABCG2 Charge Models for Drug Design Applications","authors":"Piero Procacci","doi":"10.1002/jcc.70444","DOIUrl":"10.1002/jcc.70444","url":null,"abstract":"<p>The accurate parameterization of drug-like molecules is a fundamental prerequisite for molecular dynamics simulations in structure-based drug design. While the AM1-BCC charge model has served as the <i>de facto</i> “standard” for GAFF2 parameterization for two decades, the recently introduced ABCG2 model offers substantially improved accuracy in predicting hydration free energies and other key physicochemical properties. However, accessing ABCG2 parameters traditionally requires downloading and installing the full AmberTools suite—a multi-gigabyte software package with complex dependencies—presenting a significant barrier for many practitioners, particularly experimental collaborators and researchers new to the field. Here we present a major upgrade to the PrimaDORAC web interface that makes ABCG2 parameterization readily accessible to the entire drug design community. Through a minimalistic integration of essential AmberTools components directly into the web application framework, users can now obtain GAFF2 parameters with ABCG2 charges for any drug-like molecule in seconds, without any software installation. The interface accepts a single SMILES string or structure file and returns a complete archive containing GROMACS-compatible topology files and a ready-to-use PDB structure. By removing all technical barriers to accessing state-of-the-art ABCG2 parameters, the upgraded PrimaDORAC interface is aimed at empowering medicinal chemists, pharmacologists, and computational researchers alike to conduct more accurate MD simulations with minimal effort. The service is freely available at www1.chim.unifi.it/orac.</p>","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"47 17","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcc.70444","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148275121","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":"An Energy-Corrected Fast Post-SCF Local-Hybrid Scheme for Highly Accurate Energy Differences of Large Main-Group Systems","authors":"Artur Wodyński,&nbsp;Martin Kaupp","doi":"10.1002/jcc.70431","DOIUrl":"10.1002/jcc.70431","url":null,"abstract":"<p>Local-hybrid (LH) density functionals admix exact exchange locally in real space and thereby can be powerful tools to ameliorate the usual zero-sum game between reducing self-interaction errors and modeling static correlation. But as with other hybrid functionals the practical use of LHs for large systems is limited by the cost of evaluating exact-exchange quantities self-consistently. Here we introduce an energy-corrected local-hybrid framework, EC(LH)@(m)GGA, in which a computationally expedient semi-local reference density is used for a single post-SCF evaluation with an advanced LH. Using the recent neural-network-based LH25nP LH as a prototype, we show that the EC route based on GGA or meta-GGA orbitals preserves the characteristic accuracy profile of the parent local hybrid and reaches state-of-the-art rung 4 performance on the GMTKN55 test suite (WTMAD-2 around 2.4–2.7 kcal/mol, depending on grid). The top performance of LH25nP for spin-restricted bond dissociation as a strong-correlation measure is retained in this framework. The dominant post-SCF overhead in timing is governed by the EC grid. For the practical gridsize 3, the total EC(LH)@(m)GGA cost is only about ~2–3× that of a GGA single point, typically about an order of magnitude less than a full LH SCF. Overall, EC(LH)@(m)GGA provides a simple post-SCF route to state-of-the-art rung-4 energetics at a cost close to semi-local DFT, applicable to large systems.</p>","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"47 17","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcc.70431","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148256747","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":"Correction to “Origin-Dependence of Dipole Moments of Charged Proteins: Theoretical Foundations and Implications, Revisited”","authors":"","doi":"10.1002/jcc.70435","DOIUrl":"10.1002/jcc.70435","url":null,"abstract":"<p>\u0000 <span>I. K. Matar</span> and <span>C. F. Matta</span>. “ <span>Origin-Dependence of Dipole Moments of Charged Proteins: Theoretical Foundations and Implications, Revisited</span>”. <i>Journal of Computational Chemistry</i> <span>46, no. 25 (2025): e70207,</span> https://doi.org/10.1002/jcc.70207.\u0000 </p><p>The authors apologize for these errors.</p>","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"47 16","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcc.70435","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148248270","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":"Transferable Semiempirical Models for Judd–Ofelt Parameters and Multiphonon Relaxation in Eu3+ Complexes: Toward an Experiment-Free Luminescence Design","authors":"Claudio M. B. Neto,&nbsp;Gabriel S. Santos,&nbsp;Leonardo A. de Souza,&nbsp;Lippy F. Marques,&nbsp;José D. L. Dutra,&nbsp;Ricardo O. Freire","doi":"10.1002/jcc.70438","DOIUrl":"10.1002/jcc.70438","url":null,"abstract":"<p>The rational design of lanthanide-based luminescent systems using purely theoretical approaches remains challenging due to the reliance of existing models on experimental data. Herein, we propose a theoretical protocol for the design of new Eu³⁺ based luminescent systems, starting from a previously synthesized and experimentally characterized complex. The approach is based on two semiempirical models: (i) a combination of the <i>QDC</i> and BOM models for the calculation of Judd–Ofelt intensity parameters (Ω₂ and Ω₄) and (ii) a model based on the van Dijk–Schuurmans equation and Fermi's golden rule to estimate nonradiative emission rates (<i>A</i>_NR) from radiative rates (<i>A</i>_R). The model for calculating the Judd–Ofelt intensity parameters was parameterized using the [Eu₂(Ibf)₆(bpy)₂] complex as a reference and validated with the analogous complexes [Eu₂(Ibf)₆(4,4′-dmbpy)₂] and [Eu₂(Ibf)₆(5,5′-dmbpy)₂]. In contrast, due to its mathematical structure, the model for calculating A_NR required the inclusion of all three systems in the parameterization set. The models reproduce the intensity parameters with average errors below 4% and the nonradiative rate with errors below 0.2%. The protocol was applied to eight new complexes obtained by substituting the bipyridine methyl group with NH₂, NO₂, OCH₃, and OH at the 4,4′-and 5,5′-positions. The theoretical predicted luminescent properties indicate that methoxy-substituted systems are predicted to exhibit superior performance, with predicted quantum yields of ~93.8%. This protocol provides a computationally efficient strategy for the rational design of Eu³⁺ based luminescent materials.</p>","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"47 16","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcc.70438","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148248409","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":"Development and Validation of CHARMM Force Field Parameters for Major Phytochemicals of Phyllanthus emblica","authors":"Neha Arya,&nbsp;Vaibhav Charde,&nbsp;Vijay Kumar,&nbsp;Anagha Ranade,&nbsp;Ajay K. Meena,&nbsp;Narayanam Srikanth,&nbsp;Rabinarayan Acharya,&nbsp;Sairam S. Mallajosyula","doi":"10.1002/jcc.70391","DOIUrl":"10.1002/jcc.70391","url":null,"abstract":"<div>\u0000 \u0000 <p>Polyphenolic phytochemicals derived from <i>Phyllanthus emblica</i> (amla) exhibit diverse chemical functionalities that are poorly represented in existing biomolecular force fields, limiting reliable molecular simulations of their structure and interactions. Here, we report the systematic development and validation of an all-atom, additive CHARMM force-field parameter set for major <i>Phyllanthus emblica</i> phytochemicals, including gallic acid, ellagic acid, quinic acid, ascorbic acid, ethyl gallate, and their relevant ionized forms. Parameterization was performed following established CHARMM protocols using high-level quantum mechanical reference data, with targeted fragmentation and model-compound strategies employed to address challenging conjugated and polyphenolic motifs. The optimized parameters accurately reproduce quantum mechanical conformational energetics, hydrogen-bonding interactions, and vibrational characteristics, exhibiting low deviations in both energies and geometries. Further validation is demonstrated through molecular dynamics simulations of experimentally resolved crystal structures and long-timescale protein–ligand complexes, where the parameters preserve structural stability and native interaction patterns. This work expands the chemical space accessible to CHARMM-based simulations and provides a robust, transferable framework for realistic molecular modeling of structurally complex natural products relevant to biomolecular recognition and function.</p>\u0000 </div>","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"47 16","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148222185","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":"Quantitative Assessment of Metal–Ligand Bonding in Halide-Containing Terpyridine Pincer Complexes of Group 10 Metals","authors":"Yasin Gholiee","doi":"10.1002/jcc.70441","DOIUrl":"https://doi.org/10.1002/jcc.70441","url":null,"abstract":"<div>\u0000 \u0000 <p>This study investigates metal–ligand bonding in planar pincer complexes [(tpy)M(X)]⁺, where M is Ni(II), Pd(II), or Pt(II) and X is a halide, using DFT and energy decomposition analysis. It shows that electrostatic interactions dominate the overall stability, while interaction strength decreases from fluoride to iodide. Orbital interactions contribute significantly (44.4%–50.2%) to the total attraction and are analyzed in detail under C_2v symmetry through a₁, a₂, b₁, and b₂ components, revealing different metal–ligand overlap patterns. σ-type interactions are the main orbital contribution (62.7%–76.1%), followed by π interactions (19.4%–29.6%), including in-plane and out-of-plane components. δ-type interactions are minor (4.8%–7.7%) but arise from metal–ligand π* overlap. Charge transfer trends from ligand to metal correlate well with both electrostatic and total interaction energies, supporting a consistent bonding description across the series.</p>\u0000 </div>","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"47 16","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148238082","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":"Synergistic Heavy-Atom and Vibronic-Coupling Effects for High-Performance Ionic TADF Emitters: A Theoretical Study","authors":"Yizi Meng,&nbsp;Ziye Ning,&nbsp;Bowen Tang,&nbsp;Yanying Zhang,&nbsp;Leilei Cui,&nbsp;Xiaoning Liu,&nbsp;Lingling Lv","doi":"10.1002/jcc.70445","DOIUrl":"10.1002/jcc.70445","url":null,"abstract":"<div>\u0000 \u0000 <p>Ionic thermally activated delayed fluorescence (iTADF) materials are promising for organic optoelectronics due to their solution processability and structural tunability, yet the synergistic regulation of reverse intersystem crossing (RISC) by heteroatom anchoring, heavy-atom effects, and vibronic coupling remains underexplored. Four molecules (AC-TPPO⁺, AC-TPPS⁺, AC-TPPO[Br], and AC-TPPS[Br]) are systematically investigated via density functional theory (DFT), TD-DFT, and excited-state dynamics. All molecules feature twisted donor-acceptor conformations, enabling spatial separation of frontier molecular orbitals and a small singlet–triplet energy gap (Δ<i>E</i>_ST) for RISC. The bromide counterion (Br⁻) induces a heavy-atom effect, enhancing spin-orbit coupling strength and accelerating RISC rates by two orders of magnitude. Low-to-medium-frequency vibrations further facilitate RISC by driving S₁ and T₁ potential energy surfaces to near-degeneracy. The optimal AC-TPPO[Br] achieves a high delayed fluorescence quantum yield (<i>Φ</i>_DF = 74.88%) with nearly 100% room-temperature TADF contribution. This work provides a synergistic design paradigm and theoretical guidance for high-performance OLED emitters.</p>\u0000 </div>","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"47 16","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148222249","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":"Structure-Based Design of Isoxazolidine RIPK1 Inhibitors for Neuroinflammation","authors":"Shamima Rahman Shila,&nbsp;Mansour H. Almatarneh,&nbsp;Humaera Noor Suha,&nbsp;Istiak Hossain,&nbsp;Sahar Abdalla,&nbsp;Md Ahsan Ul Bari,&nbsp;Raymond A. Poirier,&nbsp;Kabir M. Uddin","doi":"10.1002/jcc.70411","DOIUrl":"10.1002/jcc.70411","url":null,"abstract":"<div>\u0000 \u0000 <p>Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive impairment and neuronal loss. Aberrant activation of receptor-interacting protein kinase 1 (RIPK1) plays a critical role in neuroinflammation and programmed neuronal death, making it an attractive therapeutic target. In this computational study, 16 isoxazolidine derivatives (<b>1</b>–<b>16</b>) were evaluated alongside seven reference inhibitors to identify potential RIPK1 blockers. Molecular docking analyses revealed that compound <b>7</b> exhibited the highest binding affinity toward RIPK1 (PDB ID: 7XMK), with a binding energy of −9.0 kcal mol⁻¹, outperforming established inhibitors and demonstrating broad activity against AD-related targets. Density functional theory calculations showed a HOMO–LUMO energy gap of 5.209 eV, indicating favorable electronic stability. Compound <b>7</b> complied with Lipinski's rule of five and Veber's criteria and displayed excellent predictive ADMET properties, including high human intestinal absorption (HIA = 1.0), strong blood–brain barrier permeability (BBB = 0.991), and low predicted toxicity. Molecular dynamics (MD) simulations conducted over 100 ns at temperatures ranging from 300 to 320 K confirmed the stability of the RIPK1–compound <b>7</b> complex. The root-mean-square deviation (RMSD) values ranged from 5.2 to 14.0 Å (0.52–1.40 nm), indicating acceptable structural fluctuations throughout the simulation. Additionally, the radius of gyration (Rg) ranged from 2.8 to 3.8 nm, indicating that the complex maintained a relatively stable, compact conformation throughout the simulation. Principal component analysis further supported these findings, yielding cosine similarity values of 0.86–0.95. Collectively, these results highlight compound <b>7</b> as a promising RIPK1 inhibitor with favorable pharmacokinetic, electronic, and dynamic properties, underscoring its potential as a therapeutic candidate for AD.</p>\u0000 </div>","PeriodicalId":188,"journal":{"name":"Journal of Computational Chemistry","volume":"47 16","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148215906","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}