Journal of molecular graphics & modelling最新文献

{"title":"Experimental and computational analysis of benzothiophene as a selective inhibitors of diabetes mellitus","authors":"Shoaib Khan ,&nbsp;Mujaddad Ur Rehman ,&nbsp;Tayyiaba Iqbal ,&nbsp;Zanib Fiaz ,&nbsp;Parham Taslimi ,&nbsp;Hany W. Darwish ,&nbsp;Muhammad Adnan","doi":"10.1016/j.jmgm.2025.109010","DOIUrl":"10.1016/j.jmgm.2025.109010","url":null,"abstract":"<div><div>Diabetes mellitus results in chronic hyperglycemia, affecting more than one hundred million people over the world. To treat diabetes mellitus, novel benzothiophene-derived thiadiazole analogues <strong>(1-17)</strong> were synthesized to biological assess their potential as lead inhibitors of both diabetic enzymes (α-amylase and α-glucosidase). These compounds showed quite remarkable potency against both enzymes and emerged as anti-diabetic agents. As a reference for their biological assessment, acarbose (<strong>5.90 ± 0.30</strong> μM, <strong>6.50 ± 1.80</strong> μM) were used and in comparison to it analogue <strong>3 having IC₅₀ of 4.20 ± 0.50 μM, 4.90 ± 1.50 μM</strong>, <strong>6 with IC₅₀ of 3.10 ± 1.20 μM, 4.10 ± 0.80 μM</strong>, <strong>10</strong> with <strong>IC₅₀ of 5.20 ± 1.20 μM, 6.10 ± 2.10 μM</strong> and <strong>16 having IC₅₀ of 3.90 ± 2.20 μM, 4.10 ± 1.20 μM</strong> emerged as most active analogues among the synthesized derivatives. Versatile attached functionalities such as CF₃, F, OH and Cl bind with the target proteins in order to inhibit their normal activity or function. Binding potency (interactive properties) of the leading compounds was also revealed under molecular docking. ADME analysis further unveiled that the potent compounds exhibit drug properties. Moreover, reactivity of these analogues with leading potential was also explored via density functional theory (DFT), revealing their molecular electrostatic potential, electrophilic, nucleophilic, HOMO and LUMO sites.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"138 ","pages":"Article 109010"},"PeriodicalIF":2.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143714503","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":"Targeting OPA1 protein for therapeutic intervention in autosomal dominant optic atrophy: In silico drug discovery","authors":"Azhar Iqbal ,&nbsp;Muhammad Sajid ,&nbsp;Guendouzi Abdelkrim ,&nbsp;Ammara Riaz ,&nbsp;Umar Farooq ,&nbsp;Shabana Bibi ,&nbsp;Ghadeer M. Albadrani ,&nbsp;Muath Q. Al-Ghadi ,&nbsp;Amany A. Sayed ,&nbsp;Mohamed M. Abdel-Daim","doi":"10.1016/j.jmgm.2025.109013","DOIUrl":"10.1016/j.jmgm.2025.109013","url":null,"abstract":"<div><div>Autosomal dominant hereditary optic atrophy (ADOA) is a prevalent hereditary condition characterized by the gradual and simultaneous deterioration of vision. Mutations in Optic atrophy 1 (<em>OPA1</em>) have been linked to ADOA, the prevailing form of inherited optic neuropathy. However, the current therapeutic options are limited. This study aimed to identify a drug-like molecule that can serve as an activator of the <em>OPA1</em> GTPase domain, using in silico virtual screening and molecular dynamic simulation pipeline. A ligand-based pharmacophore model was generated to identify the important biological entities in natural compounds, followed by virtual screening pipeline. Total 55,96,00 drug-like compounds were screened and then subsequently proceed for molecular docking, molecular dynamics simulation (200ns), MM-PBSA analysis, and ADMET (Swiss ADME server) studies. Virtual screening revealed the top-ranked compound ZINC000009190697 (−8 kcal/mol). Furthermore, the stability of the top hit compound at the active site of <em>OPA1</em> was demonstrated using molecular dynamics simulations and MM-PBSA calculations. ADMET analysis assisted in the identification of the top hit compound as possible activators of <em>OPA1</em> with optimal drug-like properties. These results indicated that there is need of further experimental assessment of the top-hit compound ZINC000009190697 in wet lab to confirm its efficacy as a potential <em>OPA1</em> activator in both in vitro and in vivo studies.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"138 ","pages":"Article 109013"},"PeriodicalIF":2.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143680350","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":"Hydrogen storage in graphitic carbon nitride coordinated with boron clusters: A DFT study","authors":"Blanca Alicia Guardado Villegas ,&nbsp;Roberto García Carrillo ,&nbsp;Nora Aleyda García ,&nbsp;Paul Horley ,&nbsp;Mario Sánchez","doi":"10.1016/j.jmgm.2025.109021","DOIUrl":"10.1016/j.jmgm.2025.109021","url":null,"abstract":"<div><div>The search for novel materials capable of adsorbing molecular hydrogen is of great interest due to the urgent need to replace polluting fossil fuels with clean energy sources. This study evaluates the adsorption of hydrogen molecules using computational methods, specifically density functional theory (M06-2X) combined with the def2-TZVP basis set, in complexes formed with graphitic carbon nitride, gC₃N₄, and boron clusters (B_n, n = 1–6). The average adsorption energy values for the B–H₂ interactions range from −0.11 to −0.08 eV. To assess the spontaneity of these adsorption processes, Gibbs free energies were calculated for the temperatures 50–400 K. The results indicate that gC₃N₄B_n complexes can adsorb from 2 to 7 hydrogen molecules. Calculations confirm that adsorption remains spontaneous across the temperature range studied, which makes the gC₃N₄B_n complexes promising for hydrogen storage applications.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"138 ","pages":"Article 109021"},"PeriodicalIF":2.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143680352","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":"Efficient TF-IDF method for alignment-free DNA sequence similarity analysis","authors":"Emre Delibaş","doi":"10.1016/j.jmgm.2025.109011","DOIUrl":"10.1016/j.jmgm.2025.109011","url":null,"abstract":"<div><div>This study proposes a pioneering alignment-free approach for the analysis of DNA sequence similarity. The method employs the representation of DNA sequences as <em>n</em>-grams, a technique that involves the adaptation of the Term Frequency-Inverse Document Frequency (TF-IDF) algorithm to genomic data. The primary objective of this approach is to enhance the accuracy of the results while concomitantly reducing the computational costs of the process, by ascertaining the most informative <em>n</em>-grams. The approach adopted in this study successfully circumvents the limitations of both traditional alignment-based and alignment-free methods, thereby demonstrating a commendable level of performance. The proposed method was tested on three different datasets and achieved high agreement with reference phylogenetic trees in the AFProject benchmark system. The results demonstrate that TF-IDF-based similarity matrices effectively capture phylogenetic relationships and significantly reduce processing time. The high accuracy rates obtained prove that the method offers a scalable and robust alternative in large genomic datasets. The method demonstrates considerable potential in DNA sequence similarity analysis, exhibiting high accuracy and low computational cost.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"137 ","pages":"Article 109011"},"PeriodicalIF":2.7,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662477","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":"Effect of metal ions in Baijiu on cluster formation of water, ethanol, acetic acid and ethyl acetate molecules: Molecular dynamics and density functional theory studies","authors":"Chen Manjiao ,&nbsp;Jiang Qianxi ,&nbsp;Yu Jinlong ,&nbsp;Lin Zhoujun ,&nbsp;Hu Xinjun ,&nbsp;Tian Jianping","doi":"10.1016/j.jmgm.2025.109020","DOIUrl":"10.1016/j.jmgm.2025.109020","url":null,"abstract":"<div><div>Metal ions in Baijiu play an important role in the formation of liquor flavor, but their molecular mechanism has not been studied yet. In this study, molecular dynamics was used to calculate the radial distribution function (RDF), coordination number, and mean square displacement (MSD) of K⁺, Ca²⁺, and Fe²⁺ in water, ethanol, acetic acid, and ethyl acetate systems. Density functional theory was used to determine the binding energy, geometric configuration, and charge distribution of different clusters. The results of the MSD and RDF indicate that Ca²⁺ and Fe²⁺ are easily encapsulated by water or ethanol molecules in the system, resulting in weaker diffusion ability than K⁺. The interaction energy between K⁺, Ca²⁺, and Fe²⁺ and each molecule in the system increases sequentially, especially for Fe²⁺, which significantly changes the charge of molecules in the cluster. There are hydrogen bonds between molecules in clusters formed with K⁺ as the core, but there are no hydrogen bonds between molecules in clusters formed with Ca²⁺ and Fe²⁺ as the core. The cohesion of clusters formed with K⁺, Ca²⁺, and Fe²⁺ as the core increased in that order. The results of this study lay a theoretical foundation for understanding the molecular mechanism of metal ions in Baijiu.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"137 ","pages":"Article 109020"},"PeriodicalIF":2.7,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670132","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":"Computational discovery of novel PI3KC2α inhibitors using structure-based pharmacophore modeling, machine learning and molecular dynamic simulation","authors":"Bana Katrib ,&nbsp;Ahmed Adel ,&nbsp;Mohammed Abadleh ,&nbsp;Safa Daoud ,&nbsp;Mutasem Taha","doi":"10.1016/j.jmgm.2025.109016","DOIUrl":"10.1016/j.jmgm.2025.109016","url":null,"abstract":"<div><div>PI3KC2α is a lipid kinase associated with cancer metastasis and thrombosis. In this study, we present a novel computational workflow integrating structure-based pharmacophore modeling, machine learning (ML), and molecular dynamics (MD) simulations to discover new PI3KC2α inhibitors. Key innovations include the generation of diverse pharmacophores from both crystallographic and docking-derived complexes, coupled with data augmentation via ligand conformational sampling to enhance ML robustness. The optimal model, developed using XGBoost with genetic function algorithm (GFA) and Shapley additive explanations (SHAP), identified four critical pharmacophores and three descriptors governing bioactivity. Virtual screening of the NCI database using these pharmacophores yielded three hits, with <strong>H_1</strong> (NCI: 725847) demonstrating MD-derived binding stability and affinity comparable to the potent inhibitor PITCOIN1 (IC₅₀ = 95 nM). This study represents the first application of a conformation-augmented ML framework to PI3KC2α inhibition, offering a blueprint for targeting underexplored kinases with limited structural data.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"137 ","pages":"Article 109016"},"PeriodicalIF":2.7,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670129","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 of small covalent inhibitors targeting DsbA using virtual screening, covalent docking, and molecular dynamics simulations","authors":"Yuxiang Ren,&nbsp;Yuqiao Xin,&nbsp;Rongxi Zhu,&nbsp;Yang Zhang,&nbsp;Linjie Han,&nbsp;Yongshan Zhao","doi":"10.1016/j.jmgm.2025.109017","DOIUrl":"10.1016/j.jmgm.2025.109017","url":null,"abstract":"<div><div>Antimicrobial resistance (AMR) is a growing global health threat, highlighting the urgent need for new therapeutic strategies. The development of bacterial antivirulence agents and antibiotic adjuvants offers two promising strategies for combating bacterial infections. The DsbA protein is crucial for bacterial virulence and resistance, catalyzing the formation of disulfide bonds in bacterial proteins, making it an attractive target for novel antibiotics. In this study, we employed virtual screening, covalent docking, and molecular dynamics simulations to screen a library of 69,579 compounds for inhibitors targeting Cys30, a key nucleophilic residue in the CXXC catalytic motif of DsbA. We identified four small molecule covalent inhibitors that form covalent bonds with DsbA. The MM/PBSA results indicate that three covalent compounds (Cov28322, Cov16876, and Cov64052) have lower binding energies than the positive control. However, covalent binding typically offers superior target specificity and durability. These inhibitors primarily interact with key regions of DsbA, including the CXXC motif and L2 loop, suggesting their potential to disrupt DsbA's catalytic activity. This study provides a theoretical basis for designing DsbA covalent inhibitors as antibiotic adjuvants, presenting a promising strategy to combat bacterial infections and AMR.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"137 ","pages":"Article 109017"},"PeriodicalIF":2.7,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662710","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":"DFT study of pure and Pt-decorated BN nanocone as a nanocarrier for nitrosourea anticancer drug","authors":"Yousef A. Bin Jardan ,&nbsp;Fadhel.F. Sead ,&nbsp;Dharmesh Sur ,&nbsp;Suhas Ballal ,&nbsp;Abhayveer Singh ,&nbsp;T. Krithiga ,&nbsp;Aziz Kubaev ,&nbsp;Subhashree Ray ,&nbsp;Mounir M. Bekhit","doi":"10.1016/j.jmgm.2025.109018","DOIUrl":"10.1016/j.jmgm.2025.109018","url":null,"abstract":"<div><div>In this current study, the effectiveness of both the Pt-coated BN nanocone (BNC) and pristine in detecting and drug delivery of nitrosourea anticancer (NU) drugs were analyzed using periodic DFT. Research examines how the drug molecules adsorb and affect structural and electronic features of substrate. Analysis of interaction between NU and pure BNC surface, as suggested by the adsorption energy, reveals a relatively weak interaction. The adsorption energies in gas and water phases for the most stable NU@Pt-BNC complex are −1.88 eV and −2.89 eV, respectively. Study also investigated drug's ability to dissolve, along with that of surface and complexes, in an aqueous solvent. Additionally, simulations were conducted to model release of the drug from the substrate in close proximity to target cells within an acidic environment. A Pt-BNC substrate could be suggested as a promising carrier and sensor for NU anticancer medications.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"137 ","pages":"Article 109018"},"PeriodicalIF":2.7,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143636239","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":"DFT insights of the physical, optoelectronic, and energy loss function features of Cd-doped Bi2O3 oxide materials for photocatalytic applications","authors":"Farah Fahim ,&nbsp;Muhammad Ramzan ,&nbsp;Muhammad Waqas Mukhtar ,&nbsp;Zarish Nazeer ,&nbsp;Majid Niaz Akhtar ,&nbsp;Khadijah Mohammedsaleh Katubi ,&nbsp;M.S. Al-Buriahi ,&nbsp;Sami Ullah","doi":"10.1016/j.jmgm.2025.109019","DOIUrl":"10.1016/j.jmgm.2025.109019","url":null,"abstract":"<div><div>Photocatalytic water splitting is viable for sustainable H₂ production, utilizing water and solar energy through efficient photocatalysts. The first-principles method was employed to investigate the photocatalytic performance of cubic Bi2O3 comprehensively, and Cd-doped Bi2O3 structure properties were determined using the PBE-GGA functional, confirming simple cubic structure arrangement with space group 195 (P-23). Electronic analysis through total density of states (TDOS) and (PDOS) revealed significant hybridization between Bi 6s and O 2p orbitals due to doping. Moreover, charge density distributions highlighted the ionic nature of the chemical bonding, further influencing the electronic and optical properties. A key finding of this study is the observed band gap (E_g) which directly impacts the light absorption efficiency of Bi₂O₃ for water-splitting applications. The results demonstrate Cd doping effectively tailors the electronic structure, potentially enhancing photocatalytic activity. These insights provide a valuable foundation for optimizing Bi₂O₃-based materials for renewable hydrogen production.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"137 ","pages":"Article 109019"},"PeriodicalIF":2.7,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670130","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":"Novel flucytosine salt: Structure, Hirshfild surface analysis, morphology, FIMs, and computational studies","authors":"Hela Ferjani","doi":"10.1016/j.jmgm.2025.109012","DOIUrl":"10.1016/j.jmgm.2025.109012","url":null,"abstract":"<div><div>5-Flucytosine (FC) exhibits an advanced solid-state structure, which presents challenges for its pharmaceutical development. This paper presents experimental, and theoretical studies of a novel pharmaceutical salt, fluorocytosinium chloride, HFC⁺.Cl⁻. Single crystal X-ray diffraction (SCXRD) investigation indicates that HFC⁺.Cl⁻ forms crystals in the monoclinic system and <em>P</em>2₁/<em>c</em> space group. The structure is maintained by a series of hydrogen bonding interactions, comprising N-H···Cl, N-H···O, and C-H···F. In addition, noncovalent anion···π interactions between chloride anions and HFC⁺ cations play a role in establishing a three-dimensional network. Hirshfeld surface analysis (HS) and two-dimensional fingerprinting were used to enumerate the intermolecular interactions within the crystal. The results demonstrate that the H···Cl/Cl···H, O···H/H···O, and F···H/H···F interactions are the most significant. Full Interaction Maps (FIMs) analysis predicts the positions of hydrogen bond acceptors and donors, confirming the supramolecular arrangement observed in HFC⁺.Cl⁻. Computational modeling studies using the Bravais-Friedel, Donnay-Harker (BFDH), and Growth Morphology (GM) methods predict the morphology of the HFC⁺.Cl⁻ crystal. Both approaches estimate a comparable crystal shape characterized by six principal facets. Density functional theory (DFT) calculations were conducted utilizing the DMol³ software to investigate the electronic structure and comprehensive reactivity features of HFC⁺.Cl⁻. The low HOMO energy suggests significant stability against electrophilic attacks, while the high HOMO-LUMO band gap indicates high chemical hardness. Fukui functions were also calculated to identify atomic sites susceptible to nucleophilic and electrophilic attacks. This study offers a comprehensive insight into the structural and electronic properties of HFC⁺.Cl⁻, offering valuable information for the development of new pharmaceutical compositions.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"137 ","pages":"Article 109012"},"PeriodicalIF":2.7,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663369","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}