Journal of molecular graphics & modelling最新文献

{"title":"Discovery of novel microsomal prostaglandin E2 synthase 1 (mPGES-1) inhibitors by a structurally inspired virtual screening study","authors":"Abdurrahman Olğaç ,&nbsp;Paul M. Jordan ,&nbsp;Christian Kretzer ,&nbsp;Oliver Werz ,&nbsp;Erden Banoglu","doi":"10.1016/j.jmgm.2025.108962","DOIUrl":"10.1016/j.jmgm.2025.108962","url":null,"abstract":"<div><div>Prostaglandin (PG) E₂ is a pro-inflammatory lipid mediator derived from the metabolism of arachidonic acid (AA) by cyclooxygenases (COX) and PGE₂ synthases. Nonsteroidal anti-inflammatory drugs (NSAIDs), commonly used in the treatment of inflammation, nonselectively inhibit COX activity and decrease PGE₂ production. However, these drugs cause gastrointestinal bleeding and several cardiovascular complications. Therefore, inhibiting microsomal PGE₂ Synthase-1 (mPGES-1) to block PGE₂ production downstream of COX is expected to yield safer and more effective treatments for inflammation, cancer, and cardiovascular diseases. At present, there are no mPGES-1 inhibitors available on the market, but ongoing research continuously evaluates new compounds in both preclinical and clinical stages. Here, we conducted a high throughput virtual screening campaign to discover novel mPGES-1 inhibitor scaffolds. This campaign utilized physicochemical filtering alongside both structure-aware ligand-based approaches (shape screening templates and pharmacophore models, which were generated based on the 3D binding modes of the co-crystallized mPGES-1 inhibitors) and structure-based strategies (refinement with docking and molecular dynamics). Thirty-four compounds were selected and biologically tested for mPGES-1 inhibition in a cell-free assay using microsomes from interleukin-1β-stimulated A549 cells as the source of mPGES-1. The most potent compound inhibited the remaining enzyme activity with an IC₅₀ value of 6.46 μM in a cell-free assay for PGE₂ production. We also compared the binding patterns of the most active compounds identified in this study with those of co-crystallized inhibitors using molecular dynamics simulations. This comparison underscored the crucial role of ionic interactions, π-π interactions, hydrogen bonds, and water bridges involving specific amino acids. Our results highlight the importance of these interaction networks within the binding cavity in various binding scenarios. Ultimately, the insights gained from this study could assist in designing and developing new mPGES-1 inhibitors.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"136 ","pages":"Article 108962"},"PeriodicalIF":2.7,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080351","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 molecular characterization of a cyanobacterial lytic polysaccharide monooxygenase","authors":"Rodrigo Virgolino ,&nbsp;Andrei Siqueira ,&nbsp;Juliana Cassoli ,&nbsp;Délia Aguiar ,&nbsp;Evonnildo Gonçalves","doi":"10.1016/j.jmgm.2025.108970","DOIUrl":"10.1016/j.jmgm.2025.108970","url":null,"abstract":"<div><div>Lytic polysaccharide monooxygenases (LPMOs) are copper-dependent enzymes that catalyze the oxidative cleavage of β(1–4) glycosidic bonds and have attracted considerable attention because of their potential for enhancing efficiency in degrading recalcitrant polymeric substrates, in synergism with hydrolytic enzymes. Fungal-derived LPMOs are the most prevalent type, while other taxonomic groups have been described as potential alternative sources of these enzymes. In the present study, we aimed to identify and characterize <em>in silico</em> a LPMO of cyanobacterial origin with putative functions in chitin depolymerization. A similarity search of sequences and conservation of domains with characterized LPMOs identified a 289 amino acid protein from the cyanobacterium <em>Mastigocoleus testarum</em> (Order Nostocales), likely belonging to the CAZy-AA10 class. This protein is referred to as <em>Mt</em>LPMO10. Phylogenetic analysis revealed that <em>Mt</em>LPMO10 is homologous to the protein Tma12 from the fern <em>Tectaria macrodonta</em>, with 52.11 % sequence identity, which was the first LPMO characterized as originating from the plant kingdom. The protein tertiary structure predicted by the AlphaFold server indicates structural features common to LPMOs, such as a histidine brace formed by His31 and His132 and an immunoglobulin-like domain composed of antiparallel beta strands. Molecular dynamics (MD) simulation allowed the assessment of the enzyme-substrate affinity, using an initial pose based on literature data. The <em>Mt</em>LPMO10-chitin complex remained stable during 100ns of MD, while the <em>Mt</em>LPMO10-cellulose complex dissociated within 30ns of MD. Additionally, there was a shorter Cu(I)-H4 distance in the protein-substrate complex compared to the Cu(I)-H1 distance (averages of 6.0 ± 0.7 Å and 7.9 ± 0.7 Å, respectively), suggesting a C4 regioselectivity. This study highlights the existence of lytic polysaccharide monooxygenases in cyanobacteria and paves the way for further investigations related to this enigmatic class of enzymes and their potential use in biotechnological applications.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"136 ","pages":"Article 108970"},"PeriodicalIF":2.7,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143149858","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":"Exploring the electronic structure, mechanical stability and optoelectronic responses of arsenic-based M2AsX (M = Nb, Mo and X = C, N) MAX phase ceramics","authors":"Mubashar Ali ,&nbsp;Zunaira Bibi ,&nbsp;Tehreem Fatima ,&nbsp;Shamsa Kanwal ,&nbsp;Houbing Huang ,&nbsp;Bakar Bin Khatab Abbasi ,&nbsp;Munirah D. Albaqami","doi":"10.1016/j.jmgm.2025.108965","DOIUrl":"10.1016/j.jmgm.2025.108965","url":null,"abstract":"<div><div>This study utilizes first-principles computations to examine the electronic structure, mechanical stability, and optoelectronic responses of arsenic-based <span><math><mrow><msub><mi>M</mi><mn>2</mn></msub><mtext>AsX</mtext></mrow></math></span> (M = Nb, Mo and X = C, N) ceramics. We assessed the stability of these compounds by calculating their formation enthalpies and phonon dispersion curves, which showed that all the compounds we examined are stable and can be synthesized successfully. The robustness of these materials was also analyzed using elastic constants, which further confirmed that the <span><math><mrow><msub><mi>M</mi><mn>2</mn></msub><mtext>AsX</mtext></mrow></math></span> phases are stable and not prone to mechanical instability. Furthermore, the ductility or brittleness of the studied <span><math><mrow><msub><mi>M</mi><mn>2</mn></msub><mtext>AsX</mtext></mrow></math></span> compounds have been assessed by some other mechanical parameters such as Pughs and Poisson ratio, Cauchy pressure, and anisotropy factors. The acquired band structures and density of states demonstrate the metallic nature of all <span><math><mrow><msub><mi>M</mi><mn>2</mn></msub><mtext>AsX</mtext></mrow></math></span> compounds. Additionally, we have explored the several optical attributes <span><math><mrow><msub><mi>M</mi><mn>2</mn></msub><mtext>AsX</mtext></mrow></math></span> compounds in order to understand how these compounds interact with incoming electromagnetic radiation. The remarkable features of <span><math><mrow><msub><mi>M</mi><mn>2</mn></msub><mtext>AsX</mtext></mrow></math></span> compounds are expected to render them suitable for a range of applications.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"136 ","pages":"Article 108965"},"PeriodicalIF":2.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080353","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":"Molecular insight into transport properties of Troger's base based polyimide membrane","authors":"Feng Gu ,&nbsp;Yunqin Xiao ,&nbsp;Wenxiu Zou ,&nbsp;Shenshen Li ,&nbsp;Zhaohui Wang ,&nbsp;Qinghua Wang ,&nbsp;Jijun Xiao","doi":"10.1016/j.jmgm.2025.108966","DOIUrl":"10.1016/j.jmgm.2025.108966","url":null,"abstract":"<div><div>Molecular Dynamics (MD) simulations were employed to investigate the transport properties of three polyimides comprising various diamines and dianhydrides. The diamines were 2,8-diamine-4,10-dimethyl-6H,12H-5,11-methanodibenzo[b,f][1,5]diazocine (TB1) and 3,9-diamine-4,10-dimethyl-6H,12H-5,11-methanodibenzo[b,f][1,5]diazocine (TB2); the dianhydrides were 4,4’-(hexafluoroisopropylidene) diphthalic anhydride (6FDA) and 4,4′-oxydiphthalic anhydride (ODPA). And the three polyimides were denoted as p-TB1-6FDA, p-TB1-ODPA and p-TB2-6FDA, respectively. The simulations provided the properties of the bulk polyimides such as glass transition temperature, fractional free volume, and solubility parameter. The results obtained were generally in consistent with experimental findings, which validated the quality of the model construction. Diffusion coefficient of carbon dioxide (CO₂) in polyimide membrane was extracted based on mean square displacement analysis. Further research on backbone dihedral distribution and radial distribution function unveiled that Troger (TB1 or TB2) bases exerted strong influence on intra-chain mobility, 6FDA components were evenly distributed in polyimide matrix thus inhibiting inter-chain packing and CO₂ molecules in free volume are surrounded by layers formed by Oxygen/Nitrogen atoms.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"136 ","pages":"Article 108966"},"PeriodicalIF":2.7,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143149856","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":"Exploring the effect of Zr/B ratio on the stability and reactivity of activated ε-caprolactone complexes: A DFT, QTAIM and NCI study","authors":"Wijitra Meelua ,&nbsp;Tanchanok Wanjai ,&nbsp;Jitrayut Jitonnom","doi":"10.1016/j.jmgm.2025.108960","DOIUrl":"10.1016/j.jmgm.2025.108960","url":null,"abstract":"<div><div>Monomer insertion, leading to the formation of an activated monomer complex, is a critical step in cationic ring-opening polymerization (CROP) of cyclic monomers, such as ε-caprolactone (CL). In this study, Density Functional Theory (DFT) calculations were employed to investigate the structural and electronic properties of four activated complexes at two Zr:B ratios (1:2 and 1:1), where Zr is the cationic zirconocene catalyst, Cp₂ZrMe⁺, and B is the borate cocatalyst, [MeB(C₆F₅)₃]^‒ or [B(C₆F₅)₄]^‒. Steric hindrance at the reactive site was analyzed using topographic steric maps, while inter- and intramolecular interactions of the complex systems were examined through the Quantum Theory of Atoms in Molecules (QTAIM) and non-covalent interaction (NCI) analyses. The 1:2 ratio exhibited significant steric hindrance above and below the monomer plane, restricting access to the Cp₂ZrMe⁺ catalytic site and potentially limiting monomer insertion. In contrast, the 1:1 ratio displayed reduced steric congestion and stronger localized attractive forces at the catalytic site, facilitating better interactions with monomers and solvents. Conceptual DFT descriptors revealed that 1:1 systems had smaller HOMO-LUMO energy gaps, lower hardness, and higher electrophilicity, with 1:1@[B(C₆F₅)₄]⁻ identified as the most reactive complex. QTAIM identified key hydrogen bonding interactions, and the Zr-O_CL bonds, distinguishing stability and reactivity across Zr:B ratios. These findings provide valuable insights into the steric and electronic effects on monomer-activated species, enabling the optimization of Zr:B ratios and cocatalyst conditions for improved polymerization efficiency.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"136 ","pages":"Article 108960"},"PeriodicalIF":2.7,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066029","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":"Elucidating the impact of S-adenosylmethionine and histamine binding on N-methyltransferase conformational dynamics: Insights from an in silico study","authors":"Qi Chu ,&nbsp;Shuyang Sun ,&nbsp;Congcong Li ,&nbsp;Ge Qu ,&nbsp;Zhoutong Sun","doi":"10.1016/j.jmgm.2025.108961","DOIUrl":"10.1016/j.jmgm.2025.108961","url":null,"abstract":"<div><div>S-adenosylmethionine (SAM)-dependent histamine N-methyltransferase (HNMT) is a crucial enzyme involved in histamine methylation, playing an important role in the epigenetic modification of biology. It entails the addition of methyl groups to histamine molecules, thereby regulating gene expression, cellular signal transduction, and other biological processes. Therefore, gaining a profound understanding of the detailed mechanism underlying HNMT-mediated methylation reactions is instrumental in elucidating the role of histamine methylation in biology. This study employed molecular dynamics (MD) simulations to assess the mechanism of cooperative catalytic reaction between the substrate-binding domain (S domain) and the cofactor-binding domain (C domain) of HNMT. The results indicated that the interplay between the cofactor (SAM) and the C domain was mostly unaltered by substrate Histamine (HSM) binding. Nevertheless, SAM binding could induce conformational changes in the S domain, thus creating a favorable environment for substrate recognition and catalysis. Additionally, key amino acid residues that significantly contributed to substrate binding were identified based on molecular mechanics-generalized Born surface area (MM/GBSA) calculations. These findings could serve as a theoretical basis for the design of potential inhibitors and modulators targeting HNMT.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"136 ","pages":"Article 108961"},"PeriodicalIF":2.7,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065965","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":"O-H/N-H bond dissociation energies in 1,4-hydroquinone, 4-hydroxydiphenylamine, N,N′-diphenyl-1,4-phenylenediamine, and their phenoxyl and aminyl radicals","authors":"Sergey L. Khursan ,&nbsp;Mikhail Yu. Ovchinnikov ,&nbsp;Vladimir T. Varlamov","doi":"10.1016/j.jmgm.2025.108959","DOIUrl":"10.1016/j.jmgm.2025.108959","url":null,"abstract":"<div><div>Gas phase bond dissociation energies (<em>BDE</em>) O-H/N-H in hydroquinone (<strong>H</strong>_{<strong>2</strong>}<strong>Q</strong>), 4-aminophenol (<strong>AP</strong>), 1,4-phenylenediamine (<strong>PDA</strong>), 4-hydroxydiphenylamine (<strong>HDPA</strong>), N,N′-diphenyl-1,4-phenylenediamine (<strong>DPPDA</strong>) as well as in their phenoxyl/aminyl radicals have been determined using a combined technique of quantum chemical calculation. The technique included a series of DFT (PBE1PBE, TPSSTPSS, M06-2X), <em>ab initio</em> (DLPNO-CCSD(T)) methods with valence 3ξ-basis sets, composite methods of Gaussian family (G4) and Weizmann theory with <em>ab initio</em> Brueckner Doubles (W1BD), as well as reference reactions of different levels of structural similarity. W1BD method was used in combination with isodesmic reactions for <em>BDE</em> estimation (kJ∙mol⁻¹) of compounds with the only aromatic fragment: <em>BDE</em>_O-H = 352.3 (<strong>H</strong>_{<strong>2</strong>}<strong>Q</strong>), 340.0 (<strong>AP</strong>), <em>BDE</em>_N-H = 371.2 (<strong>AP</strong>), 364.1 (<strong>PDA</strong>) – in molecules; and <em>BDE</em>_O-H = 230.4 (<strong>H</strong>_{<strong>2</strong>}<strong>Q</strong>), 228.8 (<strong>AP</strong>), <em>BDE</em>_N-H = 260.0 (<strong>AP</strong>), 257.1 (<strong>PDA</strong>) – in corresponding radicals. These values were further applied to estimate the <em>BDE</em>s in <strong>HDPA</strong> and <strong>DPPDA</strong> within the homodesmotic reference process and less resource-intensive <em>ab initio</em> methods: <em>BDE</em>_O-H = 341.4 (<strong>HDPA</strong>), <em>BDE</em>_N-H = 352.9 (<strong>HDPA</strong>), 351.3 (<strong>DPPDA</strong>) for molecules; <em>BDE</em>_O-H = 237.4 (<strong>HDPA</strong>), <em>BDE</em>_N-H = 247.4 (<strong>HDPA</strong>), 252.6 (<strong>DPPDA</strong>) for radicals. DFT methods give similar results but a slightly larger standard error of calculation. The found values of <em>BDE</em>(O-H/N-H) are compared with literature data; the effect of solvation on <em>BDE</em>s is discussed.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"136 ","pages":"Article 108959"},"PeriodicalIF":2.7,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066035","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 of pure and Si-decorated boron nitride allotrope Irida monolayer as an effective sensor for hydroxyurea drug","authors":"Chou-Yi Hsu ,&nbsp;Mohammed Hashim Mohammed ,&nbsp;Dharmesh Sur ,&nbsp;Suhas Ballal ,&nbsp;Abhayveer Singh ,&nbsp;T. Krithiga ,&nbsp;Subhashree Ray ,&nbsp;Hayder Ridha-Salman ,&nbsp;Abdulrahman A. Almehizia","doi":"10.1016/j.jmgm.2025.108958","DOIUrl":"10.1016/j.jmgm.2025.108958","url":null,"abstract":"<div><div>Investigating effective nanomaterials for the detection of hydroxyurea anticancer drugs is essential for promoting human health and safeguarding environmental integrity. This research utilized first-principles estimations for examining the adhesion and electronic characteristics of hydroxyurea (HU) on both pristine and Si-decorated innovative two-dimensional boron nitride allotrope, known as Irida analogous (Ir-BNNS). Analyzing the adsorption energy revealed that the HU molecule has a significant interaction (E_ad = −1.27 eV) with the Si@Ir-BNNS, whereas it has weak interaction P-Ir-BN. Moreover, the analysis of the electron density distributions was conducted to investigate the microcosmic interaction mechanism between HU and Ir-BNNS. The Si@Ir-BNNS was highly sensitive to HU due to the observable alterations in the electrical conductance and magnetism. At ambient temperature, the Si@Ir-BNNS had a recovery time of 5.96 ms towards HU molecules. The DFT estimations can be conducive to exploring the applications of Si@Ir-BNNS in effectively sensing HU.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"136 ","pages":"Article 108958"},"PeriodicalIF":2.7,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065951","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":"Leveraging molecular dynamics, physicochemical, and structural analysis to explore OMP33-36 protein as a drug target in Acinetobacter baumannii: An approach against nosocomial infection","authors":"Sukriti Singh ,&nbsp;Jyotsna Agarwal ,&nbsp;Anupam Das ,&nbsp;Mala Trivedi ,&nbsp;Kshatresh D. Dubey ,&nbsp;K.V. Athish Pranav ,&nbsp;Manish Dwivedi","doi":"10.1016/j.jmgm.2025.108956","DOIUrl":"10.1016/j.jmgm.2025.108956","url":null,"abstract":"<div><div>The <em>Acinetobacter baumannii</em> is a member of the \"ESKAPE\" bacteria responsible for many serious multidrug-resistant (MDR) illnesses. This bacteria swiftly adapts to environmental cues leading to the emergence of multidrug-resistant variants, particularly in hospital/medical settings. In this work, we have demonstrated the outer membrane protein 33-36 (Omp33-36) porin as a potential therapeutic target in <em>A. baumannii</em> and the regulatory potential of phytocompounds using an <em>in-silico</em> drug screening approach. Omp33-36 protein receptor was retrieved from the protein data bank and characterized as a receptor protein. The possible compounds (ligands) from three plants namely <em>Andrographis paniculata, Cascabela thevetia</em>, and <em>Prosopis cineraria</em>, were evaluated for their potential against bacterial infections based on prior investigations and selected for further analysis. Initially, seventy potential phytocompounds were identified and retrieved from IMPPAT database, followed by Physio-chemical characterizations and toxicity assessment using swissADME and ProTox server respectively. 15 compounds have shown significant drug-likeliness and were implemented for their interaction analysis with Omp33-36 using Autodock Vina. The docking study presented seven compounds with the best binding affinities, ranging from −7.2 kcal/mol to −7.9 kcal/mol and further, based on the potential of these compounds, 4 phytocompounds were introduced for molecular dynamic simulation for 200ns. During MD simulation, compounds Prosogerin, Quercitin and Tamarixetin have shown a substantial affinity for the Omp33-36 protein and binding energy ranging from −18 to −33 kcal/mol. Overall, the analysis depicted the two compounds, Quercitin and Tamarixetin, with the most consistent interactions and indicated promise as drug leads in regulating <em>A. baumannii</em> infection. However, <em>in-vitro</em> and <em>in-vivo</em> experimental validation are required to propose the selected phytomolecules as a therapeutic lead against <em>A. baumannii</em>.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"136 ","pages":"Article 108956"},"PeriodicalIF":2.7,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143038733","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 modeling of the anti-inflammatory complexes of IL37","authors":"Inci Sardag ,&nbsp;Zeynep Sevval Duvenci ,&nbsp;Serkan Belkaya ,&nbsp;Emel Timucin","doi":"10.1016/j.jmgm.2025.108952","DOIUrl":"10.1016/j.jmgm.2025.108952","url":null,"abstract":"<div><div>Interleukin (IL) 37 is an anti-inflammatory cytokine belonging to the IL1 protein family. Owing to its pivotal role in modulating immune responses, elucidating the IL37 complex structures holds substantial therapeutic promise for various autoimmune disorders and cancers. However, none of the structures of IL37 complexes have been experimentally characterized. This computational study aims to address this gap through molecular modeling and classical molecular dynamics simulations. We modeled all protein–protein complexes of IL37 using a range of methods from homology modeling to AlphaFold2 multimer predictions. Models that successfully recapitulated experimental features underwent further analysis through molecular dynamics simulations. As positive controls, binary and ternary complexes of IL18 from PDB were included for comparison. Several key findings emerged from the comparative analysis of IL37 and IL18 complexes. IL37 complexes exhibited higher mobility than the IL18 complexes. Simulations of the IL37-IL18R<span><math><mi>α</mi></math></span> complex revealed altered receptor conformations capable of accommodating a dimeric IL37, with the N-terminal loop of IL37 contributing significantly to complex mobility. Additionally, the glycosyl chain on N297 of IL18R<span><math><mi>α</mi></math></span>, which contours one edge of the cytokine binding surface, acted as a steric block against the N-terminal loop of IL37. Further, investigations into interactions between IL37 and IL18BP suggested that a binding mode homologous to IL18 was unstable for IL37, indicating an alternative binding mechanism. Altogether, this study accesses to the structure and dynamics of IL37 complexes, revealing the structural underpinnings of the IL37’s modulatory effect on the IL18 signaling pathway.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"136 ","pages":"Article 108952"},"PeriodicalIF":2.7,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143039620","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}