Journal of molecular graphics & modelling最新文献

{"title":"DFT and machine learning integration to predict efficiency of modified metal-free dyes in DSSCs","authors":"Mohammed Madani Taouti ,&nbsp;Naceur Selmane ,&nbsp;Ali Cheknane ,&nbsp;Noureddine Benaya ,&nbsp;Hikmat S. Hilal","doi":"10.1016/j.jmgm.2025.108975","DOIUrl":"10.1016/j.jmgm.2025.108975","url":null,"abstract":"<div><div>Power conversion efficiency (PCE) prediction in dye-sensitized solar cells (DSSCs) increasingly relies on computation and machine learning, lowering experimental demands and accelerating materials discovery. In this work we incorporated quantum-chemical descriptors, computed via density-functional theory (DFT), with cheminformatic descriptors generated using the Mordred library to train two machine learning models. The Random Forest and XGBoost models were trained on a dataset of 40 dyes, together with their literature experimental PCEs. The model stabilities were investigated using multiple random state configurations (30, 38, 42 and 50). The trained models were used to evaluate newly engineered dyes, and then validated through electronic structure analysis. The novel dyes are derivatives of: (E)-10-methyl-9-(3-(10-methylacridin-9(10H)-ylidene)prop-1-en-1-yl)acridin-10-ium (C-PE3), 10-methyl-9-((1E,3E)-5-(10-methylacridin-9(10H)-ylidene)penta-1,3-dien-1-yl)acridin-10-ium (C-PE5) and 10-methyl-9-((1E,3E,5E)-7-(10-methylacridin-9(10H)-ylidene)hepta-1,3,5-trien-1-yl)acridin-10-ium (C-PE7). A <em>R</em>² = 0.8904 and RMSE = 0.0038 for XGBoost as performer under the random state of 38 were achieved. Both models, XGBoost and RF identified C3-PE5 and C3-PE7 as top promising candidates, with predicted PCEs of 5.49 % and 5.43 %, respectively. By integrating DFT/cheminformatics and machine learning techniques, this study enabled PCE prediction with no need for experimental input.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"136 ","pages":"Article 108975"},"PeriodicalIF":2.7,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143387833","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":"Thermodynamics of homolytic C–H bond cleavage in proteinogenic α-amino acids: Zwitterions in aqueous solution","authors":"Dagmar Štellerová,&nbsp;Erik Klein,&nbsp;Vladimír Lukeš","doi":"10.1016/j.jmgm.2025.108974","DOIUrl":"10.1016/j.jmgm.2025.108974","url":null,"abstract":"<div><div>This work provides the systematic M06-2X theoretical study of C–H bond dissociation enthalpies (BDE) in aqueous solution for 21 proteinogenic α-amino acids present in eukaryotes. The results reveal that the formation of zwitterions in an aqueous solution significantly affects the thermodynamics of the homolytic C–H bond cleavage for alpha, beta, and gamma carbon atoms. We have found that zwitterions show significantly greater stability against a free radical attack due to considerably higher enthalpies of the hydrogen atom abstraction from the C_α atom. This kind of stabilization can be beneficial during the synthesis of proteins in cells. Compared to the canonical forms, the average increase in BDE is ca. 60 kJ mol⁻¹. For all amino acids, the BDE of the most labile C–H bond was calculated using the <em>ab initio</em> G4 and G4(MP2) composite methods, as well.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"136 ","pages":"Article 108974"},"PeriodicalIF":2.7,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143387834","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":"Strategic control of electron donation in D-A-π-A dyes: Insights from DFT calculations for enhanced DSSC and NLO performance","authors":"Ruba A. Alolyan,&nbsp;Nuha Wazzan","doi":"10.1016/j.jmgm.2025.108968","DOIUrl":"10.1016/j.jmgm.2025.108968","url":null,"abstract":"<div><div>Dye-sensitized solar cells (DSSCs) are cost-effective and environmentally sustainable alternatives to traditional solar cells. In this study, two groups of novel metal-free organic (MFO) sensitizers (A1 and A2) were designed by modifying the experimentally tested WS-9 dye (E)(E)(E)-2-cyano-3-(3′-hexyl-5'-(7-(4-phenyl-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indol-7-yl)benzo[c][1,2,5]thiadiazol-4-yl)-[2,2′-bithiophen]-5-yl)acrylic acid), which has a D-A-π-A structure and a power conversion efficiency (PCE) of 9.02 %. The designed dyes incorporated two distinct donor cores -indoline (D1) and 2-diphenylaminothiophene (D2)- and a range of electron-donating groups (J to O), resulting in 12 novel dyes with enhanced electron-donating abilities. Their geometrical, optical, electronic, and electrochemical properties were studied using density functional theory (DFT) and time-dependent DFT (TD-DFT) methods, combined with the Conductor-like Polarizable Continuum Model (CPCM) to simulate solvent effects (dichloromethane). Additionally, the adsorption behavior of the dyes on TiO₂ clusters was investigated by calculating adsorption energies and analyzing UV–Vis spectra. The results show significant improvements in the dyes' intramolecular charge transfer (ICT) properties compared to the reference WS-9 dye. A maximum red-shift of 109 nm in the absorption spectrum, an extended excited-state lifetime of 4.95 ns, and lower chemical hardness were observed, accompanied by enhanced electron injection (ΔG_inj &gt; 0.2 eV) and dye regeneration (ΔG_reg &gt; 0.15 eV) efficiencies. Furthermore, the dyes exhibited large Stokes shifts (231.64–177.62 nm) and superior nonlinear optical (NLO) properties. These findings suggest that the newly designed dyes are highly promising candidates for DSSC applications, offering enhanced light-harvesting capabilities and improved photoelectrical performance.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"136 ","pages":"Article 108968"},"PeriodicalIF":2.7,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143216287","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":"Structural characterization of Aurora kinase B modulation by Epigallocatechin gallate: Insights from docking and dynamics simulations","authors":"Prashanth S. Javali,&nbsp;Kavitha Thirumurugan","doi":"10.1016/j.jmgm.2025.108973","DOIUrl":"10.1016/j.jmgm.2025.108973","url":null,"abstract":"<div><div>Aurora Kinase B (AURKB) is crucial for chromosome alignment, segregation, and cytokinesis, phosphorylating essential proteins for accurate cell division. Mutations and overexpression of AURKB are common in various cancers. Inhibiting AURKB reduces therapy resistance, making it a promising therapeutic target. Synthetic inhibitors like AZD1152 and ZM447439 show selectivity for AURKB but often lack specificity due to high homology within the aurora kinase family. Conversely, natural molecules such as flavonoids offer selectivity, lower toxicity, and potential synergy with existing chemotherapies. Investigating natural AURKB inhibitors could lead to safer and more effective cancer treatments. Epigallocatechin-3-gallate (EGCG), a catechin ester in green tea, inhibits glioma cell line proliferation by inducing spontaneous apoptosis and reduces cancer cell invasiveness by decreasing metalloproteinase, cytokine, and chemokine activities. Additionally, EGCG inhibits several kinases, including PI3K, mTOR, EGFR, and AKT, acting as an effective ATP-competitive inhibitor. Thus, EGCG may enhance the efficacy of anti-cancer therapies as an AURKB inhibitor. This study used in silico tools to predict EGCG's pharmacodynamics and pharmacokinetics, and employed AutoDock for molecular docking with AURKB. The ligand-protein complex and Apo form of AURKB were simulated for 100 ns with GROMACS using the CHARM36 force field. Free energy surface analysis and MMPBSA methods confirmed the stability and spontaneity of EGCG binding to AURKB. The conformational dynamics of the DFG (Asp-Phe-Gly) motif in AURKB upon EGCG binding revealed significant changes crucial for ATP binding and kinase activity. The distance between the phenylalanine residue of the DFG motif and the αC helix in holo AURKB increased from 14.80 Å to 23.62 Å in the lowest free energy structure, indicating a shift from the DFG-in to the DFG-out state, affecting ATP binding. The study also noted transitions in the overall protein secondary structures, such as turn to coil, coil to sheet, and coil to helix, contributing to a stable structure upon EGCG binding. These findings highlight the complex interplay between EGCG and AURKB, providing insights into the conformational dynamics and structural alterations induced by this interaction, which has implications for reducing glioma cell chemosensitivity to therapeutic drugs.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"136 ","pages":"Article 108973"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143216286","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 dynamics study of functionalized carbon nanotube loaded with multiple doxorubicin targeted to folate receptor α","authors":"Cuihong Wang ,&nbsp;Xin Gao ,&nbsp;Yue Jiang ,&nbsp;Meiling Zhang ,&nbsp;Lijuan Liu ,&nbsp;Shouchao Zhang ,&nbsp;Dan Ye ,&nbsp;Rongyun Jiang","doi":"10.1016/j.jmgm.2025.108964","DOIUrl":"10.1016/j.jmgm.2025.108964","url":null,"abstract":"<div><div>Two novel targeted drug delivery systems (DDSs) were designed: folate (FOL) conjugated (9, 9) carbon nanotube (CNT) loaded with 20 doxorubicin (DOX) molecules (FOL-CNT/20DOX) and folate (FOL) conjugated carboxylated (9, 9) CNT (COOH-CNT) loaded with 24 doxorubicin (DOX) molecules (FOL-COOH-CNT/24DOX). The targeted property to folate receptor α (FRα) was calculated using molecular dynamics (MD) calculations. The structures of the FRα/FOL-CNT/20DOX and FRα/FOL-COOH-CNT/24DOX complexes were analyzed in detail. Radial distribution functions were calculated to analyze the distribution of DOX molecules around the CNTs in the complexes. The variation of representative distances and angles between novel DDSs and FRα, number of hydrogen bonds, and secondary structures of FRα during the MD simulations were studied to analyze the dynamic properties of the novel DDSs targeted to FRα. We further analyzed the root mean square displacement and root mean square fluctuation in detail. The results indicate that the two novel DDSs were very stable and well targeted with FRα, and FOL-COOH-CNT/24DOX had better targeting and stability than FOL-CNT/20DOX. This study is expected to provide insights for the design of efficient nano drug delivery systems with good FRα targeting and controllable drug loading dosage.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"136 ","pages":"Article 108964"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143149857","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 vacancy defects in s-I clathrate hydrates","authors":"F. Mine Balcı ,&nbsp;Nevin Uras-Aytemiz","doi":"10.1016/j.jmgm.2025.108969","DOIUrl":"10.1016/j.jmgm.2025.108969","url":null,"abstract":"<div><div>This study investigates the role of vacancy defects in s-I clathrate hydrate structures, particularly in the presence of ethylene oxide (EO) molecules, through first-principles calculations. The structural properties, formation energies, and guest-host interactions of these vacancy defects were examined in both periodic systems and finite-size clusters. Our findings demonstrate that EO molecules significantly stabilize vacancy defects via hydrogen bonding, especially when forming double hydrogen bonds with dangling hydrogens (d-Hs) arising from the molecular vacancy defect. The encapsulation of EO in defect-free cages and its interaction with dangling oxygens (d-Os) were also analyzed, highlighting the superior stabilizing effect of double hydrogen bonds. These results provide new insights into the behavior of vacancy defects in hydrate structures and the potential role of polar guest molecules in enhancing defect stability and facilitating hydrate formation processes.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"136 ","pages":"Article 108969"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143216289","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":"Unravelling selectivity discrepancies of protoporphyrin binding to glutathione transferase: A comparative analysis of molecular dynamic simulated versus implicit solvent-minimized protein models","authors":"Neo Padi ,&nbsp;Sadhna Mathura ,&nbsp;Ikechukwu Achilonu","doi":"10.1016/j.jmgm.2025.108971","DOIUrl":"10.1016/j.jmgm.2025.108971","url":null,"abstract":"<div><div>Schistosomiasis is a neglected tropical disease caused by parasitic trematodes, which are an ongoing global health and veterinary concern owing to their acquired drug resistance pressure to available treatment. There is a need for a new generation of effective anthelmintics for preventive and therapeutic purposes. Natural products, such as porphyrins, have been reported to inhibit the main detoxification enzymes in these parasites, called glutathione transferases, which help them evade immune response and drug therapy, thus making them good drug targets. Computational modelling was used to screen potential inhibitors out of 461 protoporphyrin IX-like compounds, including a potent known inhibitor called bromosulfophthalein. However, unlike traditional docking, where the stable energy-minimized structure is used, a short molecular dynamic simulation step was added to yield the most averaged protein structure conformation as the starting point of high throughput virtual screening. Here, it was shown that the starting point is crucial as the results suggested different lead compounds; for the 26-kDa <em>japonicum</em> GST, the top-scoring compounds were CID: 122690402 for the minimized structure and CID: 137797052 for the MD-simulated structure. Similarly, for the 28-kDa <em>haematobium</em> GST, the lead compounds were CID: 70415734 and CID: 69301914, respectively. These results highlight the importance of incorporating protein dynamics into structure-based drug design and provide valuable insights into the development of porphyrin-based therapeutics against schistosomiasis and other helminthic infections.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"136 ","pages":"Article 108971"},"PeriodicalIF":2.7,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143349566","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":"Fosamprenavir and Tirofiban to combat COPD and cancer: A drug repurposing strategy integrating virtual screening, MD simulation, and DFT studies","authors":"Jigme Sangay Dorjay Tamang ,&nbsp;Suvankar Banerjee ,&nbsp;Balaram Ghosh ,&nbsp;Nilanjan Adhikari","doi":"10.1016/j.jmgm.2025.108967","DOIUrl":"10.1016/j.jmgm.2025.108967","url":null,"abstract":"<div><div>Matrix metalloproteinases (MMPs) are involved in different pathophysiological conditions like cancer, COPD, asthma, and inflammatory diseases. Among these MMPs, macrophage metalloelastase is one of the prime targets for COPD, and cancer. Therefore, to combat such diseases, potent novel macrophage metalloelastase inhibitors can be considered. Here, the classification-based molecular modeling was performed on large data of macrophage metalloelastase inhibitors that identified dibenzofuran, and diphenyl ether groups as important substructures contributing towards potent macrophage metalloelastase inhibition. This information was further implicated in repurposing marketed drugs through fragment-based and molecular docking-based virtual screening with molecular dynamics (MD) simulation-based stability validation and DFT calculations. This study identified fosamprenavir and tirofiban as promising hits that can exhibit potent macrophage metalloelastase inhibition which was also validated by the MD simulation and DFT-based calculations. Therefore, this study not only revealed these repurposed drugs as effective macrophage metalloelastase inhibitors but also opened up a horizon in developing novel potent macrophage metalloelastase inhibitors for the management of cancer and COPD in the future.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"136 ","pages":"Article 108967"},"PeriodicalIF":2.7,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143372468","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":"Structure-based analysis of missense mutations impacting the catalytic and substrate binding sites of hRPE65","authors":"Giulio Poli,&nbsp;Marco Macchia,&nbsp;Tiziano Tuccinardi","doi":"10.1016/j.jmgm.2025.108963","DOIUrl":"10.1016/j.jmgm.2025.108963","url":null,"abstract":"<div><div><em>h</em>RPE65 is a critical enzyme in the retinoid visual cycle and is implicated in retinal diseases caused by missense mutations that affect its function. However, many <em>h</em>RPE65 variants of uncertain significance (VUS) remain unclassified, hindering their clinical interpretation. This study aims to develop a molecular dynamics (MD)-based protocol to evaluate the pathogenicity of missense mutations located within the catalytic and substrate pockets of <em>h</em>RPE65. Using a full-length <em>h</em>RPE65 model complexed with all-<em>trans</em>-retinylpalmitate, we assessed 15 VUS for their structural and functional impacts. Our findings provide insights into the deleterious effects of these mutations, offering a framework for reclassifying VUS and identifying patients eligible for gene therapy. This approach may support clinicians in improving diagnostic precision and therapeutic decision-making for retinal diseases.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"136 ","pages":"Article 108963"},"PeriodicalIF":2.7,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080355","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":"Inhibitory mechanism of lithospermic acid on the fibrillation of type 2 diabetes associated islet amyloid polypeptide","authors":"Anisha Manchanda,&nbsp;Bhupesh Goyal","doi":"10.1016/j.jmgm.2025.108972","DOIUrl":"10.1016/j.jmgm.2025.108972","url":null,"abstract":"<div><div>The abnormal fibrillation of a 37-residue peptide hormone human islet amyloid polypeptide (hIAPP) is linked with type 2 diabetes (T2D). Pang et al. depicted a prominent role of lithospermic acid (LA) in blocking hIAPP fibrillation and alleviating the hIAPP aggregates-induced cytotoxicity. LA is a polyphenolic compound present in extra virgin olive oil with therapeutic properties. Despite its notable inhibitory effect on hIAPP fibrillation, the inhibition mechanism remains unclear. Here, molecular dynamics (MD) simulations have been utilized to shed light on the putative binding mechanism and inhibitory mechanism of LA against hIAPP fibrillation. The molecular docking predicted favourable binding (−7.1 kcal/mol) of LA with hIAPP. Interestingly, LA increases the helix content in hIAPP and blocks the conformational transition to the aggregation-competent conformations. The conformational clustering and hydrogen bond analyses depicted that LA formed hydrogen bonds with Asn21 of hIAPP, which play an important role in hIAPP aggregation. LA binds favourably to hIAPP (Δ<em>G</em>_binding = −49.62 ± 3.34 kcal/mol) with a major contribution from the van der Waals interactions. The MD simulations highlighted that LA dramatically interfered with the intrapeptide interactions and inhibited sampling of aggregation-competent β-sheet conformations in hIAPP <em>via</em> hydrogen bonds through its hydroxyl groups, van der Waals interactions with hIAPP residues, thus blocking hIAPP aggregation to β-sheet rich cytotoxic fibrillar aggregates. The MD simulations illuminated specific interactions between hIAPP and LA, which will benefit in developing new chemical entities against hIAPP fibrillation.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"136 ","pages":"Article 108972"},"PeriodicalIF":2.7,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143216288","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}