Journal of molecular graphics & modelling最新文献

{"title":"Targeting Hsp27 inhibition in Glioblastoma: A comprehensive in silico investigation","authors":"Emmanuel Amarachi Iwuchukwu,&nbsp;Ikechukwu Achilonu","doi":"10.1016/j.jmgm.2025.109132","DOIUrl":"10.1016/j.jmgm.2025.109132","url":null,"abstract":"<div><div>Glioblastoma (GBM) overexpresses heat shock protein 27 (HSP27), which enhances androgen receptor (AR) transcriptional activity. Inhibiting HSP27 can block AR signaling, offering a potential therapeutic approach for GBM. Computer analysis of structural dynamics showed that lead-optimized COMP2 and COMP3 had enhanced activity compared to COMP1, the positive control and the negative control. The re-docked ligand alignment confirms docking accuracy, while structural analysis shows that compound binding disrupts Hsp27's 3D structure, suggesting inhibition. A critical look at the ligand-bound amino acid behavior suggests slight rigidity relative to the apo, thus suggesting inactivation. Recurring observations suggest that Arg140, Arg136 and His103 are crucial for binding stabilization in the first pocket, whereas when COMP2 migrates to the second pocket, Thr143 appears to be more prominent for binding stabilization. An estimated G_bind of −31.59 ± 6.34 kcal/mol and −33.61 ± 4.09 kcal/mol was obtained for COMP1 and COMP3, respectively, whereas COMP21st and COMP2nd exhibited a G_bind of −21.96 ± 8.16 kcal/mol and −18.36 ± 5.76 kcal/mol, the positive control is −19.60 ± 4.74 and the negative control −8.45 ± 3.23; the reduction in the energy value of COMP2 in the second pocket could be due to shared pocket binding. The study suggests that COMP2 acts as a dual binder, and results from positive and negative controls indicate that the tested compounds could be HSP27 inhibitors. These compounds show promise as drug-like candidates based on pharmacokinetic and physicochemical evaluations. The findings support the development of novel HSP27 inhibitors to effectively block GLM.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"141 ","pages":"Article 109132"},"PeriodicalIF":3.0,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144896215","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":"Development of new inhibitor candidates for Sars-Cov-2 3CLpro (Main Protease): A molecular docking and molecular dynamics simulation study","authors":"Alev Arslantürk Bingul ,&nbsp;Selami Ercan ,&nbsp;Necmettin Pirinccioglu","doi":"10.1016/j.jmgm.2025.109133","DOIUrl":"10.1016/j.jmgm.2025.109133","url":null,"abstract":"<div><div>Despite the normalization in the human mobility worldwide caused by COVID-19 pandemics, the disease still remains as a major threat with emerge of new variants and therefore it is a popular target for the drug development. The 3CLpro is one of the most pivotal targets of SARS-CoV-2 which is needed for the cleavage of viral polyproteins into nonstructural proteins that are essential for viral replication. A total of 756958 molecules from ZINC15 database have been screened against 3CLpro by molecular docking. The docking scores of the top 100 ligands were in the range of −82.25 kcal/mol and −98.06 kcal/mol. Top scored nine ligands and co-crystalized <strong>N3</strong> were forwarded to the MD simulations and binding free energy studies. The binding free energy values of ligands and <strong>N3</strong> were in the range of −22.04 kcal/mol and −105.01 kcal/mol. Moreover, the binding free energy results of newly studied ligands were better than <strong>N3</strong> ligand. In addition, the docking and the MD results indicated that ligands have valuable interactions with 3CLpro binding site key residues, such as His41, Cys145 and Glu166. The ligand <strong>H03</strong> demonstrated better results than all studied ligands as well than <strong>N3</strong> for both of docking and binding free energy calculations.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"140 ","pages":"Article 109133"},"PeriodicalIF":3.0,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144772626","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 SF6 decomposition species adsorption on Ni-doped InSe Monolayer: Insights into gas sensing performance","authors":"Xiao-Qian Lin ,&nbsp;Xin Zhang ,&nbsp;Peng-Bin Pan ,&nbsp;Chuan-Fu Sun ,&nbsp;Yuan-Gen Yao","doi":"10.1016/j.jmgm.2025.109131","DOIUrl":"10.1016/j.jmgm.2025.109131","url":null,"abstract":"<div><div>This study employs first-principles calculations to investigate the gas sensing behavior of a Ni-doped indium selenide (InSe) monolayer toward four SF₆ decomposition products: H₂S, SO₂, SOF₂, and SO₂F₂. Structural optimization, AIMD, and vibrational analyses confirm the thermal stability of the Ni-InSe monolayer. Adsorption results indicate strong chemisorption for H₂S and SO₂, weak chemisorption for SOF₂, and physisorption for SO₂F₂. Notably, SOF₂ and SO₂F₂ exhibit high sensing responses (−99.5 % and −80.1 %) and rapid recovery times (6.61 × 10⁻³ s and 2.84 × 10⁻⁵ s) at room temperature, suggesting excellent reusability and selectivity. Although H₂S and SO₂ have longer recovery times at ambient temperature, their detection becomes effective at elevated temperatures. These findings highlight the potential of Ni-InSe monolayer as a stable, sensitive, and selective gas sensor for monitoring hazardous SF₆ byproducts in gas-insulated switchgear (GIS) systems.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"140 ","pages":"Article 109131"},"PeriodicalIF":3.0,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144780862","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":"Revealing the water-catalyzed activation of Chikungunya virus non-structural protein 2 (nsP2)","authors":"Emanuelly Karla Araújo Padilha ,&nbsp;Júlio Cosme Santos da Silva ,&nbsp;Edeildo Ferreira da Silva-Júnior","doi":"10.1016/j.jmgm.2025.109129","DOIUrl":"10.1016/j.jmgm.2025.109129","url":null,"abstract":"<div><div>– Chikungunya virus (CHIKV) poses a significant global health threat due to its association with debilitating arthritis and the limited therapeutic options available. Non-structural protein 2 (nsP2) is a multifunctional enzyme and cysteine protease that plays a critical role in viral replication, making it an attractive target for antiviral strategies. This study investigates the water-mediated catalytic activation mechanism of nsP2, with a particular emphasis on its catalytic role. Using density functional theory (DFT) calculations, our findings reveal that the water-mediated reaction significantly lowers the activation energy barrier. These insights provide a deeper understanding of the catalytic dynamics of nsP2, laying the groundwork for the design of inhibitors targeting this enzyme.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"140 ","pages":"Article 109129"},"PeriodicalIF":3.0,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144738661","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 insights into Li cluster–based gas sensors","authors":"Mohsen Doust Mohammadi ,&nbsp;Poonam Parkar ,&nbsp;Ajay Chaudhari","doi":"10.1016/j.jmgm.2025.109128","DOIUrl":"10.1016/j.jmgm.2025.109128","url":null,"abstract":"<div><div>Lithium clusters have emerged as promising candidates for gas sensing applications due to their tunable electronic properties and high reactivity. In this study, we systematically investigate the adsorption behaviour of CO, CO₂, CS₂, SO₂, NO, NO₂ H₂S, and NH₃ on Li clusters using Density Functional Theory (DFT). Structural and electronic analysis reveals that increasing cluster size enhances stability through stronger metallic bonding, while odd–numbered clusters exhibit spin polarization, influencing their chemical activity. Adsorption energy calculations confirm that CO, CO₂, H₂S, and NH₃ interact within the optimal energy range (0.2–0.7 eV), ensuring reversible and selective sensing. Sensitivity analysis identifies NH₃ and H₂S as the most detectable gases due to their strong charge redistribution effects. Dipole moment variations correlate with adsorption strength, further reinforcing the role of electrostatic interactions in gas detection. Density of States (DOS) and Reduced Density Gradient (RDG) analyses highlight significant electronic modifications upon gas adsorption, confirming charge transfer and interaction mechanisms. Li clusters demonstrate best performance in selectivity, adsorption energy, and recovery time for CO, CO₂, H₂S, and NH₃, making them highly promising candidates for gas sensing applications. However, competitive adsorption from H₂O, O₂, and O₂ in humid or oxygen–rich environments present challenges for real–world applications. These findings provide key insights into the gas sensing capabilities of Li clusters and pave the way for their optimization in practical sensor development.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"140 ","pages":"Article 109128"},"PeriodicalIF":2.7,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144704526","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":"Zwitterionic polymers as high-performance corrosion inhibitors: Ab-Initio quantum insights and experimental validation for iron-containing surfaces","authors":"Rodolfo Cisneros-Dévora,&nbsp;Enrique Soto-Castruita,&nbsp;Ricardo Cerón-Camacho,&nbsp;Jorge-Francisco Ramírez-Pérez,&nbsp;Eduardo Buenrostro-González,&nbsp;Mirna Pons-Jiménez,&nbsp;Fermín Rosales-Arias,&nbsp;Luis-Manuel Quej-Ake,&nbsp;José-Manuel Martínez-Magadán,&nbsp;G. Mabel Acosta-Garate,&nbsp;Raúl Oviedo-Roa,&nbsp;Luis-S. Zamudio-Rivera","doi":"10.1016/j.jmgm.2025.109127","DOIUrl":"10.1016/j.jmgm.2025.109127","url":null,"abstract":"<div><div>A polymeric-zwitterionic corrosion inhibitor (<strong>PZCI</strong>) to reduce the corrosion rate of pristine or initially degraded iron surfaces exposed to an HCl acidic aqueous medium is proposed, and its performance was both quantum-theoretically and experimentally investigated. The adsorption of HCl on iron-containing surfaces such as pyrite, hematite, siderite and pure iron was studied through Density Functional Theory (DFT) and compared with that of <strong>PZCI</strong>. DFT predicts that the quaternary-amine and carboxylate functional groups of <strong>PZCI</strong> prevent HCl from reaching the surfaces by capturing it beforehand. Likewise, the <strong>PZCI</strong>'s carboxylate oxygens bind to the degraded surfaces' exposed Fe atoms, completing the octahedral chalcogen coordination of the latter and shielding them through repulsion of approaching chlorine anions. The <strong>PZCI</strong> surface adsorption is moreover strengthened because the alkyl tail's carbon double bonds C=C are also linked by surface Fe atoms. Consequently, it is predicted that <strong>PZCI</strong> must efficiently protect surfaces at initial degradation stages against subsequent corrosion. This prediction was experimentally verified on a steel coupon immersed in HCl aqueous solutions with and without lab-synthesized <strong>PZCI</strong>, and it was found that the corrosion rate was reduced when <strong>PZCI</strong> was used.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"140 ","pages":"Article 109127"},"PeriodicalIF":2.7,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144704525","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 two variable-QSPR analysis for authentication and typification of vegetable oils","authors":"Pablo R. Duchowicz ,&nbsp;Mariano G. Mandelbaum ,&nbsp;Arturo A. Vitale ,&nbsp;Alicia B. Pomilio","doi":"10.1016/j.jmgm.2025.109126","DOIUrl":"10.1016/j.jmgm.2025.109126","url":null,"abstract":"<div><div>In the ongoing research studies on the prediction of complex chemical mixtures, the present work typifies various vegetable oils containing fatty acids in given proportions and extracted from different plant sources. This is important in the study of the properties conferred on foods, both from an organoleptic and nutritional point of view. Therefore, the ratio between the values of the saponification and iodine indices is used for the first time to carry out a Quantitative Structure-Property Relationship (QSPR) study, both parameters being the most important for characterizing oils and fats from different sources. QSPRs were formulated in 144 vegetable oils, composed of 1–8 fatty acid components. A set of 25,118 mixture descriptors was calculated as linear combinations of the non-conformational descriptors of the fatty acid components and their weight percent compositions. This approach is useful for discerning natural oils, and the Replacement Method variable subset selection technique is applied afterwards to select the best mixture descriptors in the predictive model. Finally, different vegetable oils with known composition, but unknown experimental saponification and iodine indices data, were predicted, and were successfully classified using the established QSPR. This two-variable QSPR analysis can be extended to fats and other types of oils, such as fish oils. It also serves as a background and database for other methodologies.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"140 ","pages":"Article 109126"},"PeriodicalIF":2.7,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144632013","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":"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":"Unraveling the potential targeting activity of propolis against transcriptional regulator prfA from Listeria monocytogenes to combat listeriosis","authors":"Ramya Ravindhiran,&nbsp;Kavitha Dhandapani","doi":"10.1016/j.jmgm.2025.109123","DOIUrl":"10.1016/j.jmgm.2025.109123","url":null,"abstract":"<div><div><em>Listeria monocytogenes</em> is a causative agent for pernicious listeriosis outbreaks worldwide and it has attained more alertness due to the emergence of resistance and mortality rate. A transcriptional regulator (prfA) regulates all the virulence cascades in <em>L. monocytogenes</em> making it a unique and putative target for many drug molecules. Propolis, nature's hidden treasure, is a complex and heterogeneous mixture that contains many secondary metabolites of plant origin. Bees might produce some active compounds and harnessing their bioactive potential is a burgeoning interest to treat various illnesses. In this context, the present study focuses on evaluating the targeted action of the major bioactive compounds of propolis against the putative target (prfA) of <em>L. monocytogenes</em>. Among various propolis compounds, 75 ligands were selected and docked with the A chain of prfA. Initially, the pharmacokinetic properties of the ligands were evaluated using QikProp v_5.8 in the Schrodinger suite 2023_3. All the pharmacokinetic parameters were satisfied with the selected propolis compounds and the docking score of the compounds obtained was in the range of −13.022 to −5.171 kcal/mol. The compounds with high negative docking scores, such as Ligand 70 (−13.022 kcal/mol) and Ligand 39 (−12.58 kcal/mol) were subjected to molecular dynamics simulation studies to determine their binding stability for a 100 ns simulation course using Desmond v_5.6 packages embedded in the Maestro software v_11.8, followed by the binding free energies of the ligand-receptor complexes were computed using prime MM/GBSA. All the parameters have envisaged the stability of the ligand molecules at the active site of prfA (target protein) to inhibit <em>L. monocytogenes</em> pathogenicity in the host. In sum, the compounds of propolis synergistically act against <em>L. monocytogenes</em> by actively inhibiting the activity of transcriptional regulators (prfA) to combat listeriosis outbreaks, thus ensuring food safety and public health.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"140 ","pages":"Article 109123"},"PeriodicalIF":2.7,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144611582","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}