Journal of molecular graphics & modelling最新文献

{"title":"Mechanistic insights on the antioxidant activity of selected neurotransmitters","authors":"J. Sharanya ,&nbsp;M.P. Kritik Shai ,&nbsp;Deepa Janardanan","doi":"10.1016/j.jmgm.2025.109054","DOIUrl":"10.1016/j.jmgm.2025.109054","url":null,"abstract":"<div><div>Antioxidant activity of neurotransmitters such as dopamine, serotonin, and octopamine are studied employing density functional theory at the M062X/6-311+G∗∗ level. The hydroperoxyl radical scavenging activity of these molecules is evaluated based on thermodynamic and kinetic calculations in the gas phase as well as in solvents that mimic physiological environments. The HAT mechanism is predicted to be favored in the gas phase, whereas the SPLET mechanism is preferred in water as well as in the lipid medium. Antioxidant activity of these molecules is attributed to the presence of phenolic OH groups. Dopamine is found to be the most active antioxidant in gas as well as polar medium, whereas Serotonin exhibited higher reactivity in the lipid medium. It is identified that the nature of the environment influences the antioxidant activity of these molecules. H-bonding interaction involving the vicinal OH group of the phenoxide radical is identified to be crucial towards stabilizing the radical generated from the D2 site of dopamine, making it the most reactive site of radical attack as per the HAT mechanism. Kinetic calculations of the HAT mechanism suggest that the D2 site of dopamine has the highest rate constant both in the gas phase (1.32 × 10⁶ L mol⁻¹ s⁻¹) as well as in aqueous medium (9.11 × 10³ L mol⁻¹ s⁻¹), whereas the S1 site of serotonin is predicted to be the most feasible site of attack in the lipid medium (2.15 × 10⁵ L mol⁻¹ s⁻¹). Octopamine is found to be the least reactant molecule among the three.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"138 ","pages":"Article 109054"},"PeriodicalIF":2.7,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143860573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Designing novel potent oxindole derivatives as VEGFR2 inhibitors for cancer therapy: Computational insights from molecular docking, drug-likeness, DFT, and structural dynamics studies","authors":"Sowmiya Perinbaraj ,&nbsp;Manikandan Jayaraman ,&nbsp;Jeyakanthan Jeyaraman ,&nbsp;Konda Reddy Girija","doi":"10.1016/j.jmgm.2025.109049","DOIUrl":"10.1016/j.jmgm.2025.109049","url":null,"abstract":"<div><div>Oxindole is a γ-lactam featuring a heterocyclic core, combining pyrrole and benzene rings with a carbonyl group at the second position. This scaffold is present in numerous bioactive compounds, both natural and synthetic, and has emerged as a privileged pharmacophore in medicinal chemistry due to its broad biological activity. Substitution at the 3-position of the 2-oxindole structure has been shown to enhance potency and selectivity, especially in anticancer drug development. Breast cancer, a prevalent and challenging disease affecting millions of women worldwide, underscores an urgent need for more effective treatments. Current therapies often exhibit limited efficacy, significant side effects, and resistance issues, highlighting the demand for novel drugs with improved safety profiles. This study focuses on vascular endothelial growth factor receptor-2 (VEGFR-2), an essential regulator of tumor angiogenesis, as a potential target for breast cancer therapy. Through molecular docking-based virtual screening of 360 designed oxindole derivatives, three compounds (BIATAM, CIHTAM, and IATAM) were identified as potential candidates, each demonstrating high docking scores (&gt;7 kcal/mol) and favorable interactions, including hydrogen bonding, hydrophobic contacts, and stacking. Among these, BIATAM emerged as the lead compound due to its superior docking performance, favorable pharmacokinetic profiles, and compliance with Lipinski's Rule of Five. Density functional theory (DFT) calculations confirmed its chemical stability, while molecular dynamics simulations (MDS) revealed high structural stability. Principal component-based free energy landscape (FEL) analysis highlighted limited conformational flexibility, and MM/PBSA-based binding energy calculations reinforced its strong affinity within the VEGFR-2 binding pocket. These comprehensive computational findings suggest that BIATAM holds promising potential as a novel therapeutic option for treating breast cancer.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"138 ","pages":"Article 109049"},"PeriodicalIF":2.7,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143829612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structure based prediction of selective MraY inhibitors","authors":"Sonali Chavan,&nbsp;Thomas Olsson,&nbsp;Gunnar Nyman","doi":"10.1016/j.jmgm.2025.109053","DOIUrl":"10.1016/j.jmgm.2025.109053","url":null,"abstract":"<div><div>Antibiotic resistance is becoming a growing concern of public health and hence there is an increasing demand for developing better antibiotic strategies. One such strategy includes targeting the bacterial cell wall, thereby killing the bacteria. A bacterial transmembrane enzyme MraY (Phospho-N-acetylmuramoyl-pentapeptide translocase), is considered to be a promising target for developing new antibiotics since it is involved in cell wall synthesis. Tunicamycin is an antibiotic known to inhibit the function of MraY. However, it shows cross-reactivity with the structurally homologous human enzyme hGPT (GlcNAc-1-P-transferase), which therefore calls for antibiotics with MraY selectivity. In the present computational work, we identified selective MraY inhibitors, where virtual screening of 45,411 compounds was carried out, followed by molecular dynamics simulations to check the stability of key inhibitory interactions across MraY and hGPT. From five shortlisted tentative inhibitors, comparative structural interaction analysis for both MraY and hGPT suggested three compounds as potential selective MraY inhibitors.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"138 ","pages":"Article 109053"},"PeriodicalIF":2.7,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143829611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drug delivery mechanism of isoniazid drug on Tetragonal aluminum nitride by DFT study","authors":"Heba Nawfal Al Araji ,&nbsp;Ehab Yassen Theab ,&nbsp;Shirin Shomurotova ,&nbsp;Prakash Kanjariya ,&nbsp;Asha Rajiv ,&nbsp;Aman Shankhyan ,&nbsp;Helen Merina Albert ,&nbsp;Harish Kumar ,&nbsp;Maher Ali Rusho ,&nbsp;Ahmed M. Naglah","doi":"10.1016/j.jmgm.2025.109048","DOIUrl":"10.1016/j.jmgm.2025.109048","url":null,"abstract":"<div><div>The current work employed DFT simulations to investigate both the reactivity and sensitivity of tetragonal aluminum nitride (T-AlN) as a nanocarrier towards isoniazid (INZ). The solvation effect, workfunction, quantum molecular descriptors (e.g., global softness), charge transports, and adhesion behaviour were analyzed to study the interactions between T-AlN and INZ. The adhesion of INZ onto T-AlN was robust. The adhesion energy in the aqueous phase was −21.89 kcal/mol and it was −40.56 in the gaseous phase. Based on the charge transport analyses, there was substantial charge transport throughout the adhesion. Also, there was a reduction of 59.32 % in the bandgap values for T-AlN following INZ attachment. Furthermore, the workfunction values and NBO analyses suggested that T-AlN can function as a promising nanocarrier for INZ. Additionally, the electronic attributes of T-AlN exhibited strong sensitivity towards the INH molecules. So, it is possible to use T-AlN for biosensing purposes and for tracing drugs through spectrophotometric methods in the human body.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"138 ","pages":"Article 109048"},"PeriodicalIF":2.7,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143824348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Delivery of cisplatin confined into pure and doped C240 fullerene: A molecular dynamics simulation study","authors":"Mohammad Javad Soleymani ,&nbsp;Mohsen Abbaspour ,&nbsp;Hamed Akbarzadeh ,&nbsp;Sirous Salemi","doi":"10.1016/j.jmgm.2025.109047","DOIUrl":"10.1016/j.jmgm.2025.109047","url":null,"abstract":"<div><div>In this research, we have investigated the delivery of cisplatin, as the anti-cancer drug molecule encapsulated into C240 fullerene with maximum equal number of water and carbon dioxide molecules (20H₂O+20CO₂) by continuously increasing the temperature from 310 to 450 K. We have determined the temperature at which the fullerene broke and the drug molecule released into the outer environment. To examine the effect of B, N, and Si doping of C₂₄₀ fullerene on the bond break and release temperatures, we have also simulated the 20H2O+20CO2 mixture into 3 % doped (C₂₃₃B₇, C₂₃₃N₇, and C₂₃₃Si₇) and 20 % doped (C₁₉₂B₄₈, C₁₉₂N₄₈, and C₁₉₂Si₄₈) fullerenes at the same temperature range. Our results showed that there is not any bond break and consequently the drug release for the pure fullerene containing 20H₂O+20CO₂ mixture at any temperature. It is also observed that the N-doped fullerene shows less resistance to the breakdown, especially the C₁₉₂N₄₈ fullerene. Therefore, this N-doped C₁₉₂N₄₈ fullerene is more proper compound to use in the nano drug delivery investigations using fullerene. It is also shown that the doping fullerene is a proper way to easily destruct its structure to use in the drug delivery applications. It is also shown that the self-diffusion of the cisplatin molecule is higher in the C₁₉₂N₄₈ fullerene than the other systems. This result is in agreement with the other results and approves the C₁₉₂N₄₈ fullerene for the drug delivery purpose.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"138 ","pages":"Article 109047"},"PeriodicalIF":2.7,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143829610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A density functional theory study on the adsorption of the β-lapachone anti-cancer drug onto the MB11N12 (M = au, Rh and Ru) nanoclusters as a drug delivery","authors":"Mouhssin Boulbazine ,&nbsp;Imane Djellala ,&nbsp;Abdel-Ghani Boudjahem","doi":"10.1016/j.jmgm.2025.109044","DOIUrl":"10.1016/j.jmgm.2025.109044","url":null,"abstract":"<div><div>The structural and electronic properties of the pristine and metal(M)-doped B₁₂N₁₂ (M = Ru, Rh and Au) nanoclusters were systematically analyzed using DFT calculations. The results indicate that the B₁₂N₁₂ behaves like a semiconductor with a substantial HOMO-LUMO energy gap of 6.75 eV. The introduction of the metal dopants (Ru, Rh and Au) in the pristine leads to a significant reduction of its gap energy with a variation in E_g ranging from 48.7 % to 80 %. This substantial decrease in the value of E_g underlines the crucial role that the metal can play in the electronic structure and the catalytic performance of the resulting material. The performance of the B₁₂N₁₂ cluster has been greatly improved with doping, and the doped clusters can be used in advanced technological applications. In order to explore the surface reactivity and sensing performance of the B₁₂N₁₂ nanocluster and their counterparts doped with transition metals such as Ru, Rh and Au towards the molecule cancer drugs, we systematically studied the adsorption behavior of the β-lapachone drug onto their surface. The molecule drug exhibited strong binding to B₁₂N₁₂ with adsorption energies of – 31.42 to – 40.0 kcal mol⁻¹ for the two most stable configurations. For the metal-doped B₁₂N₁₂ nanoclusters, the highest adsorption energy (– 68.0 kcal mol⁻¹) was obtained for the cluster doped by the Ru atom. The charge transfer analysis confirmed that β-lapachone gives electrons to nanoclusters, improving their chemical stability. In addition, the evaluation of the solvation energies indicates an improvement in drug delivery performance in biological environment. This study demonstrates the promise of the metal-doped B₁₂N₁₂ nanoclusters as effective carriers for the β-lapachone drug, highlighting their stability, reactivity and suitability for drug delivery applications.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"138 ","pages":"Article 109044"},"PeriodicalIF":2.7,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143825672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and investigation of hits targeting the N-methyl-D-aspartate receptor via drug repurposing: A plausible approach for anti-Alzheimer drug discovery","authors":"Nisha Bansal ,&nbsp;Mohammad Khalid Parvez ,&nbsp;M. Arockia Babu ,&nbsp;Mohammed S. Al-Dosari ,&nbsp;Thakur Gurjeet Singh ,&nbsp;Nemat Ali ,&nbsp;Yogita Tyagi ,&nbsp;Ankita Dadwal ,&nbsp;Umesh Yadav ,&nbsp;Ashish Ranjan Dwivedi","doi":"10.1016/j.jmgm.2025.109036","DOIUrl":"10.1016/j.jmgm.2025.109036","url":null,"abstract":"<div><div>The effective treatment of neurological diseases, particularly Alzheimer's disease (AD), is a significant source of frustration for drug discovery scientists. The lengthy process of drug discovery further makes this task exceedingly challenging. To enable a rapid stride in drug discovery, we focused on the drug repurposing strategy to identify new N-methyl-D-aspartate receptor (NMDAR) inhibitors from the pool of 1827 approved USFDA drugs. The high throughput virtual screening (HTVS) followed by molecular docking and molecular mechanics studies enabled us to identify two drugs, Ertugliflozin (Dock Score: −9.43 kcal/mol, MMGBSA: −104.50 kcal/mol) and Selpercatinib (Dock Score: 8.11 kcal/mol, MMGBSA: 83.62 kcal/mol), with a high affinity towards the NMDAR. The molecular dynamics analysis on these identified drugs led us to choose Ertugliflozin for its better stability as a lead for further studies. The corroboration of in silico findings led us to deduce that Ertugliflozin can inhibit NMDAR with an IC₅₀ of 613.19 nM. These results were confirmed by the anti-NMDAR ELISA-based analysis, which was further deduced via western blotting. The work is further supported by strong literature evidence that concludes the impact of antidiabetic molecules on AD progression, along with the evidence that Ertugliflozin possesses efficacy against AD with unequivocal evidence on the biological target and the mechanism. Further work, however, is required to establish this association in the in vivo or suitable model that could mimic the AD microenvironment as a part of future research.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"138 ","pages":"Article 109036"},"PeriodicalIF":2.7,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143792766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tuning charge transport in polydopamine tetramers via oxidation state and orientation in supramolecular junctions with gold contacts: An ab initio DFT study","authors":"Adrian Olejnik ,&nbsp;Robert Bogdanowicz ,&nbsp;Jacek Ryl","doi":"10.1016/j.jmgm.2025.109045","DOIUrl":"10.1016/j.jmgm.2025.109045","url":null,"abstract":"<div><div>This work presents a comprehensive computational investigation of gold-polydopamine supramolecular junctions and their electronic properties using density functional theory (DFT) and non-equilibrium Green's functions (NEGF) methodology. Non-covalent interactions between gold and PDA models are described in the slab configuration, and the molecular junction. By modulating the oxidation state, molecular structure, and surface arrangements of the PDA model, we demonstrate the tunability of the electronic structure, which is promising for application in nanodevices. Calculations reveal either metallic or n-type semiconducting behaviour depending on the oxidation state, contrasting the standard n-type characteristics of the PDA. While catechol-PDA shows an n-type semiconductor behaviour both on single Au electrodes and in the supramolecular junction configuration, quinone-PDA exhibits metallic characteristics. Moreover, magnitudes of transmission vary significantly with the structure of the PDA model. Overall, this work advances the understanding of tuning PDA electronics through interfacing with gold contacts.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"138 ","pages":"Article 109045"},"PeriodicalIF":2.7,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143792765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vibrational assignments, normal coordinates analysis, force constants, and DFT/MP2 computations of 5-Chloro-2,4,6-trifluoropyrimidine","authors":"Belal Surour ,&nbsp;Ahmed E. Hassan ,&nbsp;Honsi Anwar ,&nbsp;Tarek A. Mohamed","doi":"10.1016/j.jmgm.2025.109046","DOIUrl":"10.1016/j.jmgm.2025.109046","url":null,"abstract":"<div><div>The vibrational assignments of 5-Chloro-2,4,6-trifluoropyrimidine have been early investigated, however, the proposed fundamentals were not spanned to their appropriate species owing to neglecting the overall symmetry. Nevertheless, the lack of force constants (FCs) determination encourages us to reinvestigate the molecule. Aided by DFT (B3LYP, B3P86, B3PW91, ωBX97) and MP2 = full quantum chemical computations, we have provided a reliable vibrational analysis of all normal modes based on the C_2v point group. Different methods of the currently used normal coordinate analysis were also validated. Our results are compared with available infrared and Raman spectral data, including estimated infrared intensities, Raman scattering activities, genuine FCs in internal coordinates, and potential energy distributions (PEDs). Using NCA in a well-defined internal coordinate that enables us to estimate FCs based on G.F. Wilson led to better fundamental interpretations than those obtained from atomic displacements in Cartesian coordinates, VEDA, and MOLVIB programs. The current investigation potentially offers corrected vibrational mode assignments, filling gaps in prior literature and aiding in accurately characterizing fluorinated pyrimidine derivatives.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"138 ","pages":"Article 109046"},"PeriodicalIF":2.7,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143792768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering structural and electronic basis of silicon carbide quantum dots for photovoltaic performance: A DFT and molecular correlational analysis","authors":"Sadaf Noreen ,&nbsp;Sajjad H. Sumrra ,&nbsp;Hussein A.K. Kyhoiesh ,&nbsp;Abrar U. Hassan ,&nbsp;Ashraf Y. Elnaggar ,&nbsp;Islam H. El Azab ,&nbsp;Mohamed H.H. Mahmoud","doi":"10.1016/j.jmgm.2025.109040","DOIUrl":"10.1016/j.jmgm.2025.109040","url":null,"abstract":"<div><div>This study elucidates the structural and electronic basis of silicon carbide quantum dots (SiQs) for enhanced photovoltaic (PV) performance. We designed and optimized donor-π-acceptor Si₈C₈H₈-based SiQs using Density Functional Theory (DFT). Also, their relevant structures are collected from literature as a dataset to design their molecular descriptors by using RDKit, while their bandgaps were calculated by using PSI4 quantum chemical package. Their correlational analysis reveals that zero-order molecular connectivity (Chi0v) is the most influential parameter to strongly correlate with their maximum absorption (<em>λ</em>_max). Notably, their <em>λ</em>_max also exhibits strong correlations with Light Harvesting Efficiency (LHE) and Short-Circuit Current Density (J_sc) to indicate that longer <em>λ</em>_max can enhance their PV performance. Moderate correlations exist between Max_Abs and Open-Circuit Voltage (V_oc) and LogP and V_oc. The current findings provide insights into how structure-property relationships can guide to design high-performance SiQ based PV materials.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"138 ","pages":"Article 109040"},"PeriodicalIF":2.7,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143792767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}