Journal of molecular graphics & modelling最新文献

{"title":"Oxygen reduction reaction catalyzed by C2N nanosheet doped with a phosphorous atom: Insights from DFT calculations","authors":"Mina Shahdust ,&nbsp;Mehdi D. Esrafili ,&nbsp;Morteza Vahedpour","doi":"10.1016/j.jmgm.2025.109125","DOIUrl":"10.1016/j.jmgm.2025.109125","url":null,"abstract":"<div><div>Oxygen reduction reaction (ORR) is among the most key processes in energy conversion and storage devices like fuel cells (FCs) and batteries. Nevertheless, the slow kinetics of the ORR at the cathode electrode remains as an important challenge. In the present study, phosphorus (P)-doped C₂N monolayer is proposed as an effective and platinum-free electrocatalyst for the ORR in an acidic medium using first-principles calculations. The computed adsorption energies and charge transfers indicate that the catalytic process occurs at the P atom. Different ORR mechanisms on the P-embedded C₂N are thoroughly investigated. It is found that the electrochemical reduction of O₂ proceeds via a direct four-electron mechanism on the P-modified C₂N. Also, the ORR process on this electrocatalyst can involve both hydrogenation and dissociation pathways to yield two water molecules. Results indicate that the rate-determining step for both pathways is the generation of the first H₂O molecule, requiring an activation energy of 1.12 (dissociation) and 1.21 eV (hydrogenation). The findings presented in this study might be important for the practical development of novel and low-priced metal-free electrocatalysts in FCs.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"140 ","pages":"Article 109125"},"PeriodicalIF":2.7,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666051","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":"Characterization of a novel thermostable α-amylase from Calothrix sp. using in silico approaches","authors":"Alenna Crystiene Lima Farias de Sousa,&nbsp;Larissa Queiroz dos Santos,&nbsp;Gabriel Albuquerque Xavier,&nbsp;Délia Cristina Figueira Aguiar,&nbsp;Andrei Santos Siqueira,&nbsp;Evonnildo Costa Gonçalves","doi":"10.1016/j.jmgm.2025.109124","DOIUrl":"10.1016/j.jmgm.2025.109124","url":null,"abstract":"<div><div>Cyanobacteria, photoautotrophic microorganisms found in diverse environments, are promising producers of bioactive compounds with industrial applications. Among these, α-Amylases hydrolyze α(1,4) glycosidic bonds in starch, generating fermentable monomers for bioprocesses. This study used computational approaches to identify and characterize potentially thermostable α-Amylases from cyanobacterial sequences from a public database. The protein Amy1 was identified and analyzed through structural modeling, sequence comparison, molecular dynamics simulations, and binding free energy calculations to assess protein-ligand interactions. Molecular dynamics at 27 °C and 50 °C were conducted to evaluate putative enzyme stability, guiding experimental validation of thermostability. These studies were carried out to ensure accuracy for experimental tests, which are important to confirm this thermostable characteristic. These findings highlight cyanobacterial alpha-amylase characteristics as viable alternatives to commercial equivalents and pave the way for future biotechnological applications and large-scale production.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"140 ","pages":"Article 109124"},"PeriodicalIF":2.7,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144653580","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":"Tailoring the properties of Ti3C2 MXenes via transition metal doping for RRAM applications: Using ab-initio calculation","authors":"Tooba Aleem ,&nbsp;Muhammad Imran ,&nbsp;Fayyaz Hussain ,&nbsp;Ayesha Asma ,&nbsp;Aqsa Arooj ,&nbsp;Sarfraz Ahmad ,&nbsp;Ammar Mohamed Tighezza ,&nbsp;R.M.A. Khalil","doi":"10.1016/j.jmgm.2025.109118","DOIUrl":"10.1016/j.jmgm.2025.109118","url":null,"abstract":"<div><div>Experts consider MXene as a highly sophisticated material that can be utilized in creating effective optoelectronic gadgets due to its exceptional physical properties. Here, the theoretical aspects of the structural, phonon, thermodynamic stability, mechanical, electronic and optical properties of MXenes are computed, serving as a roadmap for scientists for developing high performance MXene based devices. The Plane Wave Augmented (PAW) method is employed within the VASP code framework to investigate the physical properties of pure MXene Ti₃C₂ and doped MXenes Ti₂XC₂, (X = Ni, Fe, Mn, and Co) yielding Ti₂NiC₂, Ti₂FeC₂, Ti₂MnC₂ and Ti₂CoC₂. The results of structural properties show that if the size of dopant atom is greater than Ti atom in Ti₃C₂, then lattice constant for that sample increases. The energy difference between spin polarized and non-spin polarized configurations, their binding energies and phonon properties are also calculated. According to the results of electronic properties, Ti₃C₂ and Ti₂NiC₂ show metallic nature while remaining samples show semiconducting behavior: Ti₂FeC₂ has bandgap of 0.21 eV, Ti₂MnC₂ has bandgap of 0.1eV and Ti₂CoC₂ shows bandgap of 0.23eV. The mechanical stability of pristine and doped MXenes is also tested using the Born Stability criteria. From Phonon symmetry points and Born stability criteria, it is evidenced that all the considered MXenes are mechanically stable. According to the results of optical properties, all MXene samples, particularly Ti₂NiC₂ has high absorption rate and low values of Loss function in the infrared region, thus appearing to be particularly appealing for optoelectronic applications, particularly RRAM devices.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"140 ","pages":"Article 109118"},"PeriodicalIF":2.7,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144587842","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":"In silico-guided exploration of SIRT6 modulation: Discovery of new fragments hits inhibitors","authors":"Ignazio Sardo ,&nbsp;Giulia Culletta ,&nbsp;Ugo Perricone ,&nbsp;Maria De Rosa ,&nbsp;Maria Rita Gulotta ,&nbsp;Virginia Spanò ,&nbsp;Marilia Barreca ,&nbsp;Clemens Steegborn ,&nbsp;Michael Weyand ,&nbsp;Marco Tutone ,&nbsp;Maria Valeria Raimondi","doi":"10.1016/j.jmgm.2025.109122","DOIUrl":"10.1016/j.jmgm.2025.109122","url":null,"abstract":"<div><div>Sirtuin 6 (SIRT6) has recently gained significant attention due to its dual role in various cancers and its involvement in crucial biological processes such as DNA damage repair, telomere maintenance, and metabolic regulation. Despite this, selective modulation of SIRT6 remains challenging, particularly regarding developing potent inhibitors. This study involved a combination of computational approaches to gain insights into the molecular mechanism of action of SIRT6 and try to identify new potential inhibitors through a virtual screening of over 25,000 molecules. We examined the structural interactions of known SIRT6 modulators using docking, molecular dynamics simulations, and binding pose metadynamics. Due to the recent findings on the SIRT6 inhibition in cancer and inflammatory diseases, we focused our attention on the inhibitors. After a structural study of the target, a fragment virtual screening (VS) allowed us to select a set of promising compounds to validate <em>in vitro</em>. Compounds 9, 10, and 13 were the most suitable for a fragment-growth strategy, paving the way for the design and synthesis of new anticancer agents targeting SIRT6.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"140 ","pages":"Article 109122"},"PeriodicalIF":2.7,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144597510","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":"Screening of Propolis compounds reveals potential inhibitors of rhinovirus 3C protease: A computational study","authors":"Hafs Essaadi ,&nbsp;Marouane Aherkou ,&nbsp;Mohammed Hakmi ,&nbsp;Ilham Kandoussi ,&nbsp;Rachid Eljaoudi ,&nbsp;Lahcen Belyamani ,&nbsp;Azeddine Ibrahimi ,&nbsp;Naima El Hafidi","doi":"10.1016/j.jmgm.2025.109121","DOIUrl":"10.1016/j.jmgm.2025.109121","url":null,"abstract":"<div><h3>Background and aim</h3><div>Rhinoviruses are major causes of respiratory infections and often aggravate conditions such as asthma. The protein 3C protease plays a crucial role as it blocks the virus replication. This study explores the potential of natural inhibitors, specifically Propolis compounds targeting the protein 3Cpro, which is a promising and less toxic alternative compared to the standard synthetic inhibitor, Rupintrivir.</div></div><div><h3>Experimental procedure</h3><div>A set of 60 propolis-derived molecules was selected and prepared for molecular docking simulations to evaluate their binding affinity to 3Cpro, then ligand-3Cpro protein interactions were visualized. A 200ns molecular dynamics (MD) simulation was conducted to assess the stability of the protein-ligand complexes, then the following MD parameters were analyzed: RMSD, RMSF, SASA, Rg, and hydrogen bonding. Binding free energies were further estimated using MM-PBSA, and per-residue energy decomposition was performed to identify key stabilizing interactions.</div></div><div><h3>Results</h3><div>The potential compounds Rutin and Retusapurpurin A displayed binding energies of −8.0 kcal/mol and −8.78 kcal/mol, respectively, outperforming the reference inhibitor Rupintrivir (−6.66 kcal/mol). MD simulations revealed that both ligands effectively stabilize 3Cpro, with RMSD scores of 1.02 ± 0.10 nm and 1,21 ± 0.22, respectively, and are also more stable in the pocket than Rupintrivir. These ligands also reduced RMSF, SASA, and Rg scores. MM-PBSA calculations showed more favorable binding energies for Rutin (−35.65 kcal/mol) and Retusapurpurin A (−31.59 kcal/mol) compared to Rupintrivir (−25.44 kcal/mol). Per-residue decomposition further revealed strong energetic contributions from catalytic site residues (His40, Glu71, and Cys147), especially in the Rutin complex.</div></div><div><h3>Conclusion</h3><div>The potential compounds Rutin and Retusapurpurin A are promising inhibitors targeting 3Cpro, exhibiting elevated potential efficacy compared to Rupintrivir. These results pave the way for the development of natural antivirals derived from Propolis and support its use as a dietary supplement for the treatment of rhinovirus infections. The chemical diversity of Propolis could limit the emergence of viral resistance. However, <em>in vitro</em> and <em>in vivo</em> experimental validation is required to confirm these observations.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"140 ","pages":"Article 109121"},"PeriodicalIF":2.7,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144556925","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":"Machine learning decision tree-based models for predicting the antibacterial activity of Lamiaceae essential oils against Staphylococcus aureus","authors":"Daniel de Oliveira Miranda ,&nbsp;Miller Santos Ferreira ,&nbsp;Albert Katchborian-Neto ,&nbsp;Renato Almeida de Oliveira ,&nbsp;João L. Baldim ,&nbsp;Tiago Branquinho Oliveira ,&nbsp;Danielle Ferreira Dias ,&nbsp;Daniela A. Chagas-Paula ,&nbsp;Marisi Gomes Soares","doi":"10.1016/j.jmgm.2025.109116","DOIUrl":"10.1016/j.jmgm.2025.109116","url":null,"abstract":"<div><div>Essential oils (EOs) are complex mixtures of volatile specialised metabolites derived from plants with well-documented antimicrobial properties. Their antibacterial activity is influenced by the composition, concentration, and synergistic interactions of their constituents. Despite their therapeutic potential, predicting the antibacterial efficacy of EOs remains scarce due to their chemical diversity and variability. This study applies computational approaches to develop predictive models for the antibacterial activity of EOs from Lamiaceae plants against <em>Staphylococcus aureus</em>. A curated dataset (NAEOL – natural antimicrobial essential oils Lamiaceae dataset) was constructed from the literature, incorporating chemical composition, Kovats index, and antibacterial activity data using minimal inhibitory concentration (MIC) values. A multi-step feature selection strategy combining ANOVA filtering, Random Forest-based variable importance ranking, and J48-based evaluation was implemented to identify robust molecular predictors. Machine learning approaches, including decision tree models (Naive-Bayes-ClassifiersTree, Random Forest, Random Tree and J48) and artificial neural networks (ANN), were employed to classify EOs as active or inactive and to investigate key patterns of bioactive compounds in their chemical composition. The models were evaluated using statistical validation metrics, and strategies for data refinement were explored to enhance the predictive performance. The J48 model assumed the best results for the predictive antibacterial activity of EOs. This model was boosted and hyper-parametrized to improve prediction performance, integrating it into an automated open KNIME workflow. Chemical compounds estragole, bicyclogermacrene, <em>o</em>-cymene, <em>γ</em>-caryophyllene, and sabinene hydrate were relevant for discriminating the presence of antibacterial activity, demonstrating the potential of computational approaches for accelerating the search for promising bioactive EOs.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"140 ","pages":"Article 109116"},"PeriodicalIF":2.7,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144580466","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":"In silico development of a broad-spectrum vaccine against ESKAPE pathogens","authors":"Mario González-Cruz ,&nbsp;Abraham Reyes-Gastellou ,&nbsp;Juan Arturo Castelán-Vega ,&nbsp;Gloria Paulina Monterrubio-López ,&nbsp;Alicia Jiménez-Alberto ,&nbsp;Gerardo Aparicio-Ozores ,&nbsp;Rosa María Ribas-Aparicio","doi":"10.1016/j.jmgm.2025.109120","DOIUrl":"10.1016/j.jmgm.2025.109120","url":null,"abstract":"<div><div>Antimicrobial-resistant ESKAPE pathogens (<em>Enterococcus faecium</em>, <em>Staphylococcus aureus</em>, <em>Klebsiella pneumoniae</em>, <em>Acinetobacter baumannii</em>, <em>Pseudomonas aeruginosa</em>, and <em>Enterobacter cloacae</em>) have significantly restricted therapeutic alternatives for critical infections, consequently contributing to increase the severity and mortality of infectious illnesses that represent a significant global health challenge. Vaccination as a preventive measure can be crucial in substantially reducing bacterial infections and is potentially effective against antibiotic-resistant bacteria. This study shows the design of an epitope-based vaccine capable of neutralizing shared antigenic determinants present among the ESKAPE pathogens. The pangenome of the ESKAPE pathogens was analyzed to extract the core proteome. This approach facilitated reverse vaccinology analysis to identify antigenic proteins within this bacterial group. The study revealed similar structures in porins OmpA, OprD, and TolC, as well as the collagen-binding adhesins Acm and Cna. These proteins were then utilized to predict T-cell and B-cell epitopes, selecting those with their best physicochemical properties, antigenicity, non-allergenicity, and lack of toxicity. Additionally, epitopes located on the surface of the antigens and capable of coupling with HLA molecules were prioritized. In this computational approach, we engineered a construct incorporating the adjuvant RS09, a TLR4 agonist, and immunogenic epitopes connected by linkers. We assessed the stability of their interaction with pattern recognition receptors of the immune system through molecular docking and molecular dynamics simulations. The <em>in silico</em> immune simulation demonstrated that the vaccine could trigger humoral and cell-mediated immune responses. The resulting construct potentially represents an effective and safe vaccine candidate to prevent infections caused by the ESKAPE group.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"140 ","pages":"Article 109120"},"PeriodicalIF":2.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144549518","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 study of toluene capture by imidazolium-based ionic liquids paired with acetate, tetrafluoroborate and hexafluorophosphate anions","authors":"Armaghan Ahmadi,&nbsp;Morteza Zare","doi":"10.1016/j.jmgm.2025.109119","DOIUrl":"10.1016/j.jmgm.2025.109119","url":null,"abstract":"<div><div>In this study, the capture of toluene by imidazolium-based ionic liquids (ILs) paired with acetate, tetrafluoroborate, and hexafluorophosphate anions was theoretically investigated. The geometries of the anions, cations, and ion pairs were analyzed, and the most stable structures for toluene adsorption were identified. The interaction energy of the ion pair–toluene complex and binding energy for the most stable structures were calculated. It was found that acetate-containing ILs exhibited the highest interaction and binding energies. For acetate-containing ILs, both the ion pair–toluene interaction energy and binding energy increased with the elongation of the alkyl chain. Molecular Electrostatic Potential (MEP) surfaces were generated to identify the ion pair sites that preferentially interact with toluene. The ion pair–toluene interactions in the most stable structures were examined using Natural Bond Orbital (NBO) analysis. Finally, non-covalent interactions between ion pairs and toluene were analyzed using Non-Covalent Interaction (NCI) analysis. This study underscores the critical influence of anion selection and alkyl chain modification in tailoring ILs for efficient toluene capture, offering valuable guidelines for the rational design of ILs in environmental and industrial applications.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"140 ","pages":"Article 109119"},"PeriodicalIF":2.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144536095","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 DFT study on degradation of aflatoxin B1 using some reactive oxygen and nitrogen species of plasma-activated water","authors":"Zahra Sankohan ,&nbsp;Ehsan Zahedi ,&nbsp;Mehrdad Ghavami ,&nbsp;Alireza Shahab Lavasani ,&nbsp;Gholamhassan Asadi","doi":"10.1016/j.jmgm.2025.109117","DOIUrl":"10.1016/j.jmgm.2025.109117","url":null,"abstract":"<div><div>The degradation mechanism of aflatoxin B1 using some reactive oxygen and nitrogen species of plasma-activated water have been investigated theoretically at the M06-2X/aug-cc-pVTZ//M06-2X/6-31G(<em>d</em>) level. Diffusion rate coefficient for all studied reactions was calculated to be ∼10⁹ M⁻¹ s⁻¹ and related activation energy was about 18–19 kJ mol⁻¹. The most favorable pathways of degradation were addition the vinyl bond of terminal furan ring. The apparent rate coefficients triggered by ^•OH, ozone, ^•O₂⁻, ^•NO, and NO₃⁻ at 298.15 K were 10⁹, 10⁴, 10⁻⁸, 10⁻⁷, and 10⁻⁴¹ M⁻¹ s⁻¹, implying that ^•OH and ozone play efficient role in the degradation while the effect of ^•O₂⁻, ^•NO, and NO₃⁻ species can be ignored. Overall activation energies associated with the apparent rate coefficients for addition of ^•OH and ozone to the vinyl bond of terminal furan ring were 17.02 and 18.96 kJ mol⁻¹, while corresponding branching ratios were 82.8 % and 86.28 %, respectively. Ecotoxicity and mutagenicity of major degradation adducts have been estimated using the quantitative structure activity relationships methodologies. Aflatoxin B1 as mutagenic compound does not show acute and chronic toxicity to earthworm and aquatic organisms but was toxic for rats. Mutagenicity of the most abundant oxidation products was negative while the toxicity of them was less than AFB1.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"140 ","pages":"Article 109117"},"PeriodicalIF":2.7,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144536094","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 1-O-Galloyl -β-D-glucose as a potent activator of Sirtuin-1: an in-silico study","authors":"Shanitha Abdul Vahid ,&nbsp;Manu Sudhakar ,&nbsp;Achuthsankar S. Nair ,&nbsp;Saja Kamalamma","doi":"10.1016/j.jmgm.2025.109114","DOIUrl":"10.1016/j.jmgm.2025.109114","url":null,"abstract":"<div><div>Sirt-1 is a deacetylase acting on histones and various non-histone proteins, playing a crucial role in multiple physiological and pathological processes. Scientific efforts to regulate its activity primarily focus on small molecule activators. In order to identify better small molecular natural compounds activating Sirt-1, this study employed traditional knowledge-driven in silico studies based on phytochemicals from selected medicinal plants. Molecular docking studies against Sirt-1 using a phytochemical library, identified 1-O-galloyl-β-D-Glucose (GBDG) that binds to the allosteric site of Sirt-1 with docking score, H-bond interaction and other docking features better than that of resveratrol, a known natural small molecular activator of Sirt-1. Molecular dynamic simulation of the docked complex, followed by trajectory analysis (RMSD, RMSF, Radius of Gyration and binding energy) demonstrated that the complex is structurally and thermodynamically stable. Centroid distance measurement between key residues in the regulatory and catalytic domain revealed that docking of GBDG resulted in change in conformation fetching catalytic domain closer to the regulatory domain. GBDG docking against Sirt-1 increased its affinity to the acetylated substrate as indicated by better docking parameters when compared with that of Sirt-1(apo) and resveratrol-Sirt-1 docked complex. The docking of GBDG to the allosteric site along with favorable docking parameters, enhanced interactions between the catalytic and regulatory domains, increased complex stability (as shown by molecular dynamics simulation), and greater binding affinity to acetylated peptide substrate suggest that GBDG is a potent allosteric regulator of Sirt-1.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"140 ","pages":"Article 109114"},"PeriodicalIF":2.7,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144482441","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}