Journal of molecular graphics & modelling最新文献

{"title":"Exploring the interaction between a LRRK2/PP1CA interfering peptide and PP1CA","authors":"Jose Dominguez-Meijde ,&nbsp;Samuel Murail ,&nbsp;Rachid Boudjelloul ,&nbsp;Angelita Rebollo ,&nbsp;Pierre Tuffery","doi":"10.1016/j.jmgm.2025.109140","DOIUrl":"10.1016/j.jmgm.2025.109140","url":null,"abstract":"<div><div>Parkinson's disease (PD) is a complex neurodegenerative disorder for which there is presently only palliative treatments. Recently, the interaction between the Leucine Reach Repeat Kinase 2 (LRRK2) and the Protein Phosphatase 1 (PP1) has come to light as a priority target for PD, but the way LRRK2 and PP1 interact is currently unknown, hampering the design of modulators. We have previously identified a fragment of LRRK2 able to interfere with the interaction of LRRK2 and PP1 catalytic subunit alpha (PP1CA), and we assume it should bind PP1CA at the LRRK2/PP1CA interface. In this study, we first identify the fragments of PP1CA that are able to interfere with the LRRK2/PP1CA interaction so as to get information about the regions of PP1CA likely to face LRRK2. Next, by combining <em>in silico</em> studies with <em>in vitro</em> competition experiments, we narrow down among the various hypotheses proposed regarding its mode of binding to PP1CA. Overall, we identify one preferred binding mode between the LRRK2 fragment and PP1CA consistent with <em>in vitro</em> results obtained for mutants of the initial fragment. These results pave the way for further rational design of modulators of the LRRK2/PP1CA interaction, to further decipher the molecular mechanisms underlying PD etiology.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"141 ","pages":"Article 109140"},"PeriodicalIF":3.0,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144906927","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 design of endothelin receptor antagonists using Monte Carlo-based QSAR modeling, molecular docking, and ADME profiling","authors":"Marija Marinković ,&nbsp;Nemanja Nikolić ,&nbsp;Tamara Nikolić ,&nbsp;Borislav Božanić ,&nbsp;Marija Topalović ,&nbsp;Andrija Rančić ,&nbsp;Stefan Šajnović ,&nbsp;Aleksandar M. Veselinović","doi":"10.1016/j.jmgm.2025.109155","DOIUrl":"10.1016/j.jmgm.2025.109155","url":null,"abstract":"<div><div>Endothelin-1 (ET-1), a potent vasoconstrictor peptide, plays a critical role in cardiovascular pathologies and remains a key target for therapeutic intervention. Despite its clinical significance, the development of selective and potent ET-1 antagonists continues to present major challenges. Computational methods, particularly Quantitative Structure–Activity Relationship (QSAR) modeling, offer a rational and efficient framework for designing such compounds. In this study, conformation-independent QSAR models were developed using molecular descriptors derived from SMILES notation and local molecular graph invariants. The Monte Carlo method was employed for descriptor selection and weight optimization, resulting in statistically robust models. Critical molecular fragments associated with antagonist activity were identified and applied in the computer-aided design (CAD) of new ET-1 inhibitors. The optimal QSAR model exhibited strong predictive performance, with high correlation coefficients for both the training set (r² = 0.9362, q² = 0.9314) and the test set (r² = 0.9006, q² = 0.8655). To further validate the structural plausibility of the designed molecules, molecular docking simulations were conducted against the ETA receptor. The docking results were in agreement with QSAR-predicted activity, revealing favorable binding poses, strong interaction energies, and consistent structure–activity trends across all six designed compounds. This methodological convergence strengthens the credibility of the in silico predictions. Additionally, computational analysis of physicochemical and pharmacokinetic parameters indicated favorable ADME profiles, high drug-likeness, and efficient gastrointestinal absorption, suggesting suitability for medicinal chemistry development. This study introduces a reliable and mechanistically interpretable computational pipeline for the discovery of novel ET-1 antagonists. The proposed compounds demonstrate promising pharmacological characteristics and represent viable candidates for future experimental validation. These findings underscore the value of integrated in silico strategies in accelerating cardiovascular drug discovery.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"141 ","pages":"Article 109155"},"PeriodicalIF":3.0,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144893268","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":"Comprehensive computational modeling and interactions mechanisms of GIPR homodimerization","authors":"Zichong Huang ,&nbsp;Limin Du ,&nbsp;Xulei Fu ,&nbsp;Fan Shi ,&nbsp;Linlin Yang ,&nbsp;Shun Xu","doi":"10.1016/j.jmgm.2025.109150","DOIUrl":"10.1016/j.jmgm.2025.109150","url":null,"abstract":"<div><div>G protein-coupled receptors (GPCRs) are transmembrane receptors that regulate intracellular signaling by interacting with G proteins and other effectors, influencing various physiological processes. The Glucose-dependent Insulinotropic Polypeptide Receptor (GIPR), a class B1 GPCR family member activated by GIP, regulates postprandial glycaemia by augmenting glucose-dependent insulin secretion, delaying gastric emptying, and suppressing appetite. Recent studies highlight the transmembrane domain (TMD) as the primary interface for dimerization, allowing GPCR to form homodimers or heterodimers with distinct physiological roles. However, the transient nature of these dimers challenges structural analysis, hindering experimental exploration and drug development. Computational methods now offer powerful tools for predicting such interactions. This study employs a hybrid approach, combining multiple protein docking software and dynamic structural optimization, to generate potential homodimeric models of GIPR-TMD. In addition, Next, validated models will provide insights into dimer activation mechanisms and support novel therapeutic discoveries.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"141 ","pages":"Article 109150"},"PeriodicalIF":3.0,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144904380","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 machine learning-gaussian process screening of carbazole based donors to design efficient organic polymers for photovoltaic applications","authors":"Hussein A.K. Kyhoiesh ,&nbsp;Ashraf Y. Elnaggar ,&nbsp;Mustafa Al-Khafaji ,&nbsp;Islam H. El Azab ,&nbsp;Nemah H.M. Al-Jubori ,&nbsp;Mohamed H.H. Mahmoud ,&nbsp;Mohammed Yaqob","doi":"10.1016/j.jmgm.2025.109154","DOIUrl":"10.1016/j.jmgm.2025.109154","url":null,"abstract":"<div><div>Rapid industrialization is creating a serious threat to natural resources due to the overuse of fossil fuels. This is not only destroying the environment, but their extinction is also expected soon. Such a situation has increased the interest of scientists in designing new photovoltaic (<em>PV</em>) materials with tailored applications. In this study, a machine learning (<em>ML</em>)-assisted approach was proposed for the identification of optimal carbazole-based donor materials aimed at increasing the efficiency of organic <em>PVs</em> (<em>OPVs</em>). An extensive dataset comprising 592 carbazole-derived organic compounds was curated from existing literature, and their open circuit voltage (<em>V</em>_<em>oc</em>), is calculated. Through a targeted analysis, the top-performing donors exhibiting the highest <em>V</em>_<em>oc</em> values are identified. These selected donors are subsequently employed to design new <em>TIC</em>-based polymers to contribute a notable enhancement of the <em>V</em>_<em>oc</em> in the resulting <em>PV</em> devices. Results demonstrate <em>ML</em> potential to accelerate the discovery and optimization of organic solar materials, paving the way for the development of more sustainable and effective <em>PV</em> technologies.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"141 ","pages":"Article 109154"},"PeriodicalIF":3.0,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144896216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and deciphering novel compounds dynamics against DTYMK: A potential oncogene against pancreatic cancer","authors":"Abdulaziz A. Aloliqi,&nbsp;Hamid G. Mohamed","doi":"10.1016/j.jmgm.2025.109141","DOIUrl":"10.1016/j.jmgm.2025.109141","url":null,"abstract":"<div><div>Deoxythymidylate kinase (DTYMK) plays a key role in the progression of pancreatic cancer (PC). The computational study began by selecting DTYMK as an anti-cancer target and using a drug library called the FDA-approved anticancer drug library, which contains 1745 compounds. Using molecular docking analysis, MD simulation, and pharmacokinetics profiling, the study identified three novel drug compounds, AZD2281, MDV3100, and carbamazepine with docking scores of −9.8 kcal/mol, −9.7 kcal/mol, and −9.6 kcal/mol, respectively. Additionally, the control compound (E)-1-(4-(hydroxy (phosphonooxy) phosphoryl) but-2-en-1-yl)-5-methyl pyrimidine-1, 3-diium-2, 4-bis (olate) showed a binding affinity of −7.3 kcal/mol. All three compounds met the Lipinski Rule of Five and were considered drug-like. The DTYMK complexes had mean RMSD values of 2.00 Å, 2.07 Å, 1.92 Å, and 2.84 Å for AZD2281, MDV3100, carbamazepine, and the control, respectively. The AZD2281 complex demonstrated the highest stability with no major deviation observed. Salt bridge analysis revealed key interactions such as Glu140-Arg14, Glu26-Arg22, Glu40-Arg37, and Asp103-Lys106. PCA analysis was performed to simplify large datasets, revealing that the eigenvalue patterns of the complexes were quite distinct. MMGB/PBSA calculations showed values of −95.96 kcal/mol and −97.36 kcal/mol for AZD2281, indicating its stability during ligand binding. The most suitable entropy value for AZD2281 suggested the most consistent and ordered binding. This in silico approach identified novel therapeutic compounds for pancreatic cancer, which still require experimental validation and may be modified for targeting DTYMK.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"141 ","pages":"Article 109141"},"PeriodicalIF":3.0,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144852280","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 novel non-covalent Mpro inhibitors against SARS-CoV-2 by the computational and experimental approaches","authors":"Chaochun Wei ,&nbsp;Keli Zong ,&nbsp;Wei Li ,&nbsp;Cong Wang ,&nbsp;Jiajun Ruan ,&nbsp;Hong Yan ,&nbsp;Ruiyuan Cao ,&nbsp;Xingzhou Li","doi":"10.1016/j.jmgm.2025.109151","DOIUrl":"10.1016/j.jmgm.2025.109151","url":null,"abstract":"<div><div>The COVID-19 pandemic, caused by SARS-CoV-2, has posed significant global health challenges and there is an urgent need for effective therapeutic agents. The main protease (M^pro) plays a crucial role in viral replication, making it an attractive target for the development of antiviral drugs. In this study, by screening over 8.06 million compounds obtained from Enamine, Vitas-M, ChemDiv, and TargetMol (USA) databases, 52 top-ranking compounds were obtained as promising candidates through molecular docking, followed by Uni-QSAR modeling and ADMET predictions to evaluate their binding affinities and pharmacokinetic properties. Biological activity assays confirmed the efficacy of four standout candidates <strong>L17</strong>, <strong>L26</strong>, <strong>L37</strong>, and <strong>L50</strong> with IC₅₀ values of 5.61 ± 0.58 μM, 6.00 ± 0.63 μM, 4.21 ± 0.89 μM, and 2.84 ± 1.20 μM, respectively, comparable to that of reference <strong>ML188</strong> (2.41 ± 0.70 μM). Further insights were gained through density functional theory (DFT) analyses, which provided valuable information regarding the electronic and structural properties of the candidate compounds. Additionally, extensive molecular dynamics (MD) simulations were conducted, revealing critical information about the stability and binding interactions of the compounds within the M^pro active site over a 500 ns simulation period. Besides, the results of binding free energy calculations demonstrated that compounds had higher binding affinity than <strong>ML188</strong>, and dcTMD simulations further revealed that <strong>L26</strong>, <strong>L37</strong>, and <strong>L50</strong> followed more favorable and cooperative unbinding pathways with higher energy barriers and lower dissipation compared to <strong>ML188</strong>. Overall, the results highlight the therapeutic potential of these compounds as effective M^pro inhibitors, laying a solid foundation for further development into novel antiviral agents against SARS-CoV-2.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"141 ","pages":"Article 109151"},"PeriodicalIF":3.0,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144889216","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":"2D TiB2 monolayer as a promising anode material for high-performance magnesium-ion batteries","authors":"Tingting Feng ,&nbsp;Dong Dong","doi":"10.1016/j.jmgm.2025.109142","DOIUrl":"10.1016/j.jmgm.2025.109142","url":null,"abstract":"<div><div>The design and fabrication of high-performance anode materials are pivotal in advancing the development of next-generation magnesium-ion batteries (MIBs). Herein, we conducted a comprehensive first-principles calculation to investigate the structure properties and electronic characteristics of the emerging TiB₂ monolayer, and further evaluate its potential as an anode material of MIBs. Our computational results reveal that the TiB₂ anode exhibits intrinsic metallic behavior and demonstrates a strong affinity for Mg ions with a notably low adsorption energy of −1.39 eV. Utilizing the crystal orbital Hamiltonian population analysis, it is found that the Mg-B bonds show distinct ionic bonding characteristics and dominate the interactions within Mg ion – TiB₂ anode interface. Mg ions can diffuse rapidly on the TiB₂ anode surface with a low diffusion barrier of 0.05 eV, which implies an excellent charging-discharge rate. Moreover, the efficient Mg adsorption on the two sides of TiB₂ anode leads to a high storage capacity of 3085.45 mA h/g and a low average open-circuit voltage of 0.39 V, superior to many reported 2D materials. The TiB₂ anode further demonstrates excellent thermal stability and tiny lattice change during the electrochemical cycling process, which is of paramount importance for achieving a prolonged cycle life. These exceptional properties reveal that TiB₂ monolayer is an appealing anode candidate for high-performance MIBs.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"141 ","pages":"Article 109142"},"PeriodicalIF":3.0,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144841133","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":"Detection of toxic aldrin and chlordane molecules using β-arsenic phosphide nanotubes – a first-principles perspective","authors":"M.S. Jyothi ,&nbsp;V. Nagarajan ,&nbsp;R. Chandiramouli","doi":"10.1016/j.jmgm.2025.109138","DOIUrl":"10.1016/j.jmgm.2025.109138","url":null,"abstract":"<div><div>Recently, a low-dimensional semiconducting material has shown great interest owing to its excellent tunable nature with regard to structural and electronic properties. Due to its tunable nature, it can be utilized in various potential applications, including chemical sensors. In the present research study, we employed β-arsenic phosphide nanotubes (β-AsP NT) as a base material to detect aldrin and chlordane pollutants, which are prominent insecticides. At first, the structural firmness is confirmed with phonon-band maps and formation energy. Furthermore, band structure and projected density of states spectrum portray the electronic properties of the β-AsP NT. The energy gap of β-AsP NT is calculated to be 1.268 eV, showing a semiconducting nature. The adsorption behaviour of these toxic pollutants on β-AsP NT is confirmed by the significant parameters, namely relative band gap changes, charge transfer analysis, and adsorption energy. The adsorption energy (−0.315 eV to −0.974 eV) within the range reveals that the pollutants are physisorbed on β-AsP NT. The maximum band gap variation is obtained upon the adsorption of target pollutants aldrin and chlordane, on the top-site of β-AsP NT. The overall outcomes suggest that the proposed β-AsP NT can be efficiently utilized as a chemo-resistive sensor to detect target pollutants under ambient conditions.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"141 ","pages":"Article 109138"},"PeriodicalIF":3.0,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144827819","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 bond kinetics and their temperature dependence of biocompatibility-based choline amino acid ionic liquids","authors":"Ying Chen ,&nbsp;Jianying Qu ,&nbsp;Xinyi Li ,&nbsp;Yanzhao Sun ,&nbsp;Ying Ma ,&nbsp;Hehui Zhang ,&nbsp;Xiang Wang","doi":"10.1016/j.jmgm.2025.109139","DOIUrl":"10.1016/j.jmgm.2025.109139","url":null,"abstract":"<div><div>Choline amino acid ionic liquids ([Ch][AA]) are green solvents with high thermal stability, good biodegradability and low toxicity. In this work, the hydrogen bond kinetic properties of the four [Ch][AA] and the effect of temperature on them were investigated using density functional theory (DFT) calculations and molecular dynamics (MD) simulations. By atom-in-molecule (AIM) and noncovalent interaction (RDG) analysis, it was found that the hydroxyl hydrogen (H_c1) atom and the methyl hydrogen (H_c2) atom of the cation form hydrogen bonds with the carboxylate oxygen (O_a) atom of the anion (O_c-H_c1···O_a hydrogen bond, C_c-H_c2···O_a hydrogen bond), respectively. However, the O_c-H_c1···O_a hydrogen bond interaction was stronger than the C_c-H_c2···O_a hydrogen bond interaction. Simultaneously, radial distribution functions (RDFs) analysis further confirmed that the O_c-H_c1···O_a hydrogen bond interaction was stronger. As chain length of anion increases, the strength of the O_c-H_c1···O_a and C_c-H_c2···O_a hydrogen bond interactions increase. Furthermore, with the increase of temperature, the interactions between the particles weaken, while the diffusion coefficient and the ionic conductivity increase. Box snapshots and Spatial distribution functions (SDFs) analysis indicated that aggregation phenomenon occurs between anions in [Ch][AA], forming clusters, which was mainly due to the side chain interaction between anions. As chain length of anion increases, this aggregation phenomenon became more evident. In addition, it was found that hydroxyl groups can participate in the formation of more hydrogen bonding networks, which enhances the intermolecular forces between the ionic liquids and makes the system more viscous.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"141 ","pages":"Article 109139"},"PeriodicalIF":3.0,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144830120","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 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}