Journal of molecular graphics & modelling最新文献

{"title":"Computational modeling of ubiquitin specific protease 7 (USP7) complexes with N-benzylpiperidinol derivatives incorporating binding site flexibility","authors":"Jorge Luis Valdés-Albuernes,&nbsp;Erbio Díaz-Pico,&nbsp;José Luis Velázquez-Libera,&nbsp;Julio Caballero","doi":"10.1016/j.jmgm.2025.109272","DOIUrl":"10.1016/j.jmgm.2025.109272","url":null,"abstract":"<div><div>Ubiquitin-specific protease 7 (USP7) is a key regulator of protein homeostasis, playing critical roles in various cellular processes, including DNA damage response, immune signaling, and oncogenesis. Targeting USP7 with small-molecule inhibitors has emerged as a promising therapeutic strategy, particularly in the context of cancer and autoimmune diseases. Among the diverse scaffolds explored for USP7 inhibition, <em>N</em>-benzylpiperidinol (NBP) derivatives have shown notable potential due to their structural versatility and bioactivity. Computationally, it is possible to access models of complexes between these inhibitors and USP7 by utilizing the crystallographic structures of USP7 available in the Protein Data Bank. In a classical approach, models of NBPs can be obtained within a rigid USP7 structure. In this work, we report models of complexes between 58 NBPs and variable conformations of USP7 using a flexible docking protocol employing the novel CorrEA method. As part of this protocol, we obtained diverse USP7 structures through molecular dynamics (MD) and selected complex models with inhibitors based on their biological activities. Model quality was validated using LigRMSD and interaction fingerprints (IFP). The flexible treatment of USP7 enabled the capture of binding-site conformational changes. These changes are critical for explaining the activity differences among the studied compounds.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"144 ","pages":"Article 109272"},"PeriodicalIF":3.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145928864","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 molecular dynamics study of PIM2 lipid bilayer membranes","authors":"Yago Mendes Paes ,&nbsp;João L.R. Scaini ,&nbsp;Vania R. de Lima ,&nbsp;Adriano Velasque Werhli ,&nbsp;Pedro Almeida da Silva ,&nbsp;José Rafael Bordin ,&nbsp;Karina dos Santos Machado","doi":"10.1016/j.jmgm.2026.109284","DOIUrl":"10.1016/j.jmgm.2026.109284","url":null,"abstract":"<div><div>Developing simplified yet representative models of the complex <em>Mycobacterium tuberculosis</em> inner membrane is crucial for advancing Molecular Dynamics of this pathogen. Phosphatidyl-myo-inositol dimannosides (PIM<span><math><msub><mrow></mrow><mrow><mn>2</mn></mrow></msub></math></span>), one of the most abundant lipids in this membrane, provides an ideal basis for such a model. In this study, we proposed a minimal, single-component atomistic PIM<span><math><msub><mrow></mrow><mrow><mn>2</mn></mrow></msub></math></span> bilayer for use in <em>M. tuberculosis</em> research. We validate the model by assessing its ability to reproduce distinct temperature-dependent ordering regimes, with a more ordered, gel-like behavior at 310 K and increased fluidity at 363.15 K, its capacity for spontaneous self-assembly, and its interaction with the native transmembrane efflux pump, Tap (Rv1258c). Our simulations confirm that the model exhibits the correct phase behavior at experimental temperatures and readily self-assembles into an extended lamellar bilayer-like structure. Importantly, the PIM<span><math><msub><mrow></mrow><mrow><mn>2</mn></mrow></msub></math></span> membrane provides a significantly more stable environment for the embedded Tap protein compared to a standard dipalmitoylphosphatidylcholine (DPPC) bilayer. These findings confirm the PIM<span><math><msub><mrow></mrow><mrow><mn>2</mn></mrow></msub></math></span> bilayer as a robust and promising model. It is particularly well suited for investigating the protein–lipid interactions central to multidrug resistance in <em>M. tuberculosis</em> and for exploring phenomena such as the bacterial immunological thermostat.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"144 ","pages":"Article 109284"},"PeriodicalIF":3.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146029906","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":"Drug repurposing strategy to identify the putative leads against the Epidermal growth factor receptor (EGFR) from the USFDA-approved drug pool: Investigating the utility as an anticancer agent","authors":"Nemat Ali ,&nbsp;Ali M. Alaseem ,&nbsp;M. Arockia Babu ,&nbsp;Thakur Gurjeet Singh ,&nbsp;Glowi Alasiri ,&nbsp;Mohammad Fareed ,&nbsp;Yogita Tyagi ,&nbsp;Nisha Bansal","doi":"10.1016/j.jmgm.2026.109310","DOIUrl":"10.1016/j.jmgm.2026.109310","url":null,"abstract":"<div><div>EGFR is a validated drug target in anticancer drug discovery. However, the existing issues of drug resistance, toxicities, and evolving mutations in EGFR have led to the global decline in the putative and potent anti-EGFR therapeutics. To address this gap, drug repurposing or repositioning is a valid technique for drug identification in a quick time and in an economical way. We herein employed the drug repurposing techniques from the library of 3500 approved USFDA small molecules. The initial HTVS (high-throughput virtual screening), followed by XP analysis and molecular mechanics (MMGBSA) and ADME profiling, led to the identification of Cycloguanil (antimalarial) and Metformin (antidiabetic) as the putative lead molecules with the potential to inhibit the EGFR. The top-scoring ligand was subjected to a molecular dynamics simulation study that stabilized the stability of cycloguanil within the ATP pocket of EGFR. The biological investigations further corroborated the in-silico studies. Cycloguanil inhibited the EGFR with a half maximal inhibitory concentration (IC50) of IC₅₀ of 490 nM compared to erlotinib with an IC₅₀ of 222 nM. Besides this, cycloguanil was able to halt the cell cycle progression at the G1 phase (46.54%), a peculiar feature of the kinase inhibitors that affect the CDKs and cyclins required for the passage of cancer cells through G1. Annexin V assay revealed that cycloguanil induced profound apoptosis in A549 cells. The lead molecules were also found to possess cytotoxicity profiles in MCF-7, A549, and HCT-116, which were reported to harbor the expression of EGFR. From the analysis, it was deduced that cycloguanil exhibited the most potent cytotoxicity towards the A549 cell with an IC50 of 6.83 μM, followed by HCT-116 with an IC50 of 9.32 μM, while in MCF-7, it exhibited an IC₅₀ of 14.82 μM. The lead molecule, cycloguanil, may plausibly serve as an important template that may be optimized by performing bioisosteric replacements, leading to a putative kinase inhibitor with a potent anticancer profile.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"144 ","pages":"Article 109310"},"PeriodicalIF":3.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146125163","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":"Evaluating the drug delivery potential of functionalized calix [4] arene for carboplatin-drug: A computational study analyzing static electric field and solvent effects through DFT, TD-DFT, and NLO techniques","authors":"M. Rezaei-Sameti,&nbsp;M. Heydari","doi":"10.1016/j.jmgm.2026.109275","DOIUrl":"10.1016/j.jmgm.2026.109275","url":null,"abstract":"<div><div>Targeted and precise drug delivery using nanomaterials remains a major goal in cancer therapy. In this study, the interaction of carboplatin, a key anticancer drug, with pristine and functionalized calix[4]arene (CHO, COOH, NH₂, NO₂) was investigated under varying solvent environments (water, ethanol, DMSO) and static electric fields (SEF) using density functional theory (DFT) at the GD3-Cam-B3LYP/Lanl2DZ level. The negative adsorption energy (E_ads) and enthalpy (ΔH) values confirm exothermic and thermodynamically favorable interactions across all complexes. Among them, CC-NO₂-II exhibits the highest E_ads (−32.54 kcal/mol in the gas phase), while CC-COOH derivatives demonstrate exceptional stability across solvents due to strong hydrogen bonding and dipolar interactions. Under SEF (z+0.05 a.u.), CC-NH₂ exhibits the most significant enhancement in E_ads (−276.01 kcal/mol), highlighting its potential for field-assisted drug delivery. The CC-COOH complex shows the greatest E_gap reduction (83.6 %), attributed to its high dipole moment and polarizability. Non-covalent interactions, including hydrogen bonding, van der Waals forces, and electrostatic interactions, were confirmed through atoms-in-molecules (AIM) and reduced density gradient (RDG) analyses. These findings underscore the potential of functionalized calix [4] arene as an efficient and tunable drug carrier, with external fields and solvents serving as effective modulation factors. This work provides valuable insights for the molecular design of advanced, field-responsive drug delivery systems for targeted chemotherapy applications.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"144 ","pages":"Article 109275"},"PeriodicalIF":3.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146079128","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 exploration of thiazole urea-based Gyr B inhibitors through different computational approaches: Bayesian classification, molecular docking and free energy-inspired molecular dynamics simulation","authors":"Yuvraj Kumar ,&nbsp;Arijit Bhattacharya ,&nbsp;Swati Dogra ,&nbsp;Manoj Kumar ,&nbsp;Mohan Lal Kori ,&nbsp;Om Silakari","doi":"10.1016/j.jmgm.2026.109316","DOIUrl":"10.1016/j.jmgm.2026.109316","url":null,"abstract":"<div><div>The emergence of multidrug-resistant (MDR) tuberculosis (TB) has posed a major challenge to global health, primarily due to resistance against first-generation fluoroquinolones targeting DNA Gyrase subunit A (Gyr A). In this context, DNA Gyrase subunit B (Gyr B), essential for bacterial DNA replication and topological regulation, has emerged as a potential alternative drug target. Despite efforts by medicinal chemists, no FDA-approved Gyr B inhibitors are currently available for TB treatment. This study adopts a comprehensive computational approach to identify key structural features responsible for Gyr B inhibition. A statistically robust Bayesian classification model was developed using thiazole-urea derivatives to uncover essential molecular fingerprints associated with Gyr B inhibitory activity. The developed model exhibited strong predictive performances with high ROC scores for both the training and test set. Molecular docking revealed critical interactions between selected inhibitors and the Gyr B active site, validating the relevance of identified fingerprints. Additionally, molecular dynamics (MD) simulations were conducted to evaluate the stability of protein-ligand complexes, with <em>RMSD</em>, <em>RMSF</em>, and <em>R</em>_<em>g</em> analyses further supported by principal component analysis (PCA), free energy landscape (FEL) analysis, and MMPBSA analysis. Based on identified fingerprints, five novel compounds were rationally designed and validated computationally. The top two designed compounds demonstrate good ADME profile with favourable binding and dynamic stability profiles, suggesting the potential for further biological assessment. The current molecular modeling pipeline offers crucial insights that may help researchers in the rational design of novel Gyr B inhibitors against MDR-TB.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"144 ","pages":"Article 109316"},"PeriodicalIF":3.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146180323","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 discovery of novel TAOK3 inhibitor via virtual screening, molecular dynamics simulations, and MM/GBSA analysis","authors":"Ali M. Alaseem ,&nbsp;Glowi Alasiri ,&nbsp;Mohamed M. El-Wekil ,&nbsp;Al-Montaser Bellah H. Ali ,&nbsp;Ahmed K. Hamdy","doi":"10.1016/j.jmgm.2026.109286","DOIUrl":"10.1016/j.jmgm.2026.109286","url":null,"abstract":"<div><div>Cancer persists as a leading cause of global mortality, and the mitogen-activated protein kinase (MAPK) pathway plays a pivotal role in tumor progression and drug resistance. Among MAPK regulators, TAOK3 has emerged as a promising therapeutic target due to its oncogenic role in various cancers. Despite its significance, no clinically approved TAOK3 inhibitors exist. In this study we implemented a structure-based virtual screening approach to identify potential TAOK3 inhibitors from a library of 10,000 lead-like compounds. Molecular docking identified ten top-ranked candidates, with compound Z1 (ZINC ID: 77585305) demonstrating the strongest binding affinity (ΔG = −8.42 kcal/mol), outperforming reported inhibitors NCGC00188382 and SBI-581. ADMET profiling confirmed Z1's favorable drug-like properties, including high gastrointestinal absorption and minimal toxicity risks. Molecular dynamics simulations (100 ns) confirmed stable binding of Z1 to TAOK3, as indicated by low RMSD (&lt;0.25 nm), consistent RMSF profiles, and compact radius of gyration. End-state free energy calculations using MM/GBSA also supported favorable binding, with Z1 showing excellent van der Waals interactions (−39.82 kcal/mol). Dynamic cross-correlation matrices and free energy landscape analysis further validated the stability of the TAOK3-Z1 complex. Collectively, these findings highlight Z1 as a promising TAOK3 inhibitor and a potential lead compound for further experimental validation in anticancer drug development.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"144 ","pages":"Article 109286"},"PeriodicalIF":3.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145980544","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":"Effects of taurine on the ion solvation scenario and its counteraction against the urea-induced denaturation of protein","authors":"Chinmay Parida,&nbsp;Pragin Chettiyankandy,&nbsp;Deepak Kumar Mahanta,&nbsp;Snehasis Chowdhuri","doi":"10.1016/j.jmgm.2026.109315","DOIUrl":"10.1016/j.jmgm.2026.109315","url":null,"abstract":"<div><div>Molecular dynamics (MD) simulations have carried out to investigate the solvation scenario of ions (Na⁺, K⁺, Cl⁻, I⁻, NH₄⁺, CH₃COO⁻) in the binary water-taurine and ternary water-taurine-urea mixtures at 308 K. The hydrogen bond (H-bond) properties and dynamics of water‒water, taurine‒water, and ammonium/acetate ion‒water are also explored. Our study revealed that monovalent cations have a higher tendency towards oxygen of taurine than water. NH₄⁺ preferably interacts with the oxygen of the sulfonate group, whereas acetate ions are attributed towards the amino-hydrogens of taurine compared to the oxygen and hydrogens of water. It is found that taurine forms stronger H-bonds with water molecules through its amino group indicating the higher donating tendency of taurine. The translational and orientational relaxation dynamics of water molecules are slowed down in both the binary and ternary mixtures. The average lifetime of the water's H-bonds is higher in the ternary mixtures than the binary mixtures. Addition of urea enhances the overall lifetime of the ammonium ion-water (H_AMM…O_WAT) and acetate ion-water (O_ACE…H_WAT) H-bonds. We have also observed that taurine counteracts the denaturation effect of urea on human islet amyloid polypeptide (hIAPP), as evidenced by the secondary structure. The α-helix content of hIAPP is restored with the addition of 0.45 M taurine in 5.60 M urea concentrations.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"144 ","pages":"Article 109315"},"PeriodicalIF":3.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146142674","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":"DeepHybridCPI: A hybrid deep learning framework for compound–protein interaction prediction","authors":"Areen Rasool,&nbsp;Jamshaid Ul Rahman,&nbsp;Qasim Ali","doi":"10.1016/j.jmgm.2026.109303","DOIUrl":"10.1016/j.jmgm.2026.109303","url":null,"abstract":"<div><div>In bioinformatics, deep learning-based methods for Compound-Protein Interaction (CPI) prediction play a vital role in virtual screening, drug discovery, and drug repositioning. Recent improvements in computational methods have shown great possibility to save costs of experiment and speed up target identification. Nevertheless, the current CPI forecasting methods remain severely limited. Many rely on shallow Graph Neural Networks (GNNs) that struggle to capture the global structural context of compounds, while conventional Convolutional Neural Networks (CNNs) focus primarily on local sequence motifs and fail to model long-range dependencies in proteins. Even though a number of recent architectures strive to solve these problems by adding complexity to models, or by adding complex modules, these additions often cause significant computational overhead. To overcome these challenges, we propose DeepHybridCPI, a hybrid deep learning framework designed for accurate and efficient CPI prediction. Our hybrid model integrates a multiscale, densely connected GNN to extract compound features capturing both local substructures and global molecular topology, and employs CNNs with Long Short-Term Memory (LSTM) networks to model both local motifs and extended dependencies in protein sequences. The learned compound and protein representations are fused into a unified latent space to enable effective interaction modeling. Experimental evaluations on benchmark Human and <em>C. elegans</em> datasets demonstrate that DeepHybridCPI consistently outperforms existing state-of-the-art baseline methods in terms of AUC, Precision, and Recall. These findings highlight the importance of combining multiscale compound representations with hybrid sequence encoders within a single unified framework, providing a promising avenue for accelerating computational drug discovery. We release our source code and dataset at: <span><span>https://github.com/jamshaidwarraich/DeepHybridCPI</span><svg><path></path></svg></span>.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"144 ","pages":"Article 109303"},"PeriodicalIF":3.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146018798","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":"Investigating the anti-Alzheimer potential of biogenic compounds from Zinc15 database as NMDA antagonist: An in-silico approach","authors":"Somdatta Chaudhari ,&nbsp;Asavari Shinde ,&nbsp;Mukund Salunke ,&nbsp;Shriram Bairagi ,&nbsp;Azad Dhage ,&nbsp;Pinkal Patel ,&nbsp;Vivek Rathod ,&nbsp;Sandeep Pathare ,&nbsp;Nojood Altwaijry ,&nbsp;Mohd Shahnawaz Khan","doi":"10.1016/j.jmgm.2026.109277","DOIUrl":"10.1016/j.jmgm.2026.109277","url":null,"abstract":"<div><div>Alzheimer's disease is an unavoidable neurological disorder in which the death of brain cells brings on memory loss, cognitive decline, and eventual dementia. There is no recognized treatment for Alzheimer's illness. By the year 2050, it is expected that the global population will witness approximately 100 million cases of Alzheimer's disease (AD). Despite recognizing AD as a formidable illness for over a century, no effective cure has been discovered thus far. Synaptic dysfunction could result from disturbed synaptic calcium handling caused by excessive activation of glutamate receptors, particularly the N-methyl-D-aspartate receptors (NMDARs). Glutamate serves as the brain's primary excitatory neurotransmitter, acting on ionotropic and metabotropic glutamate receptors. In recent years, several pharmacologically active substances derived from plants, animals, and microbes have shown promise in treating AD by focusing on various pathogenic processes. Initially, we used virtual screening to assess natural product-like compounds against NMDA receptors. In this research study, we have screened a natural compound database derived from zinc15. The best candidate was then validated through molecular dynamics simulation (MDS). The results revealed that out of 4221 compounds tested, only 165 showed superior binding interactions compared to native ligands, making them inhibitors for protein. Further analysis using ADMET indicates favorable drug-like properties, particularly for CNS drug-likeness. The MDS results, including RMSD, RMSF, Rg, and residue interactions, indicated a strong and stable association between top molecules and target protein. This confirms that top molecules can effectively remain within the binding pockets of the target proteins, forming stable protein-ligand complexes.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"144 ","pages":"Article 109277"},"PeriodicalIF":3.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146157389","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":"On QSPR analysis for predicting efficacy of physicochemical properties of antibiotics drugs via topological indices and regression models","authors":"Yingxuan Huang ,&nbsp;W. Eltayeb Ahmed ,&nbsp;Muhammad Farhan Hanif ,&nbsp;Saba Hanif ,&nbsp;Muhammad Imran ,&nbsp;Muhammad Kamran Siddiqui","doi":"10.1016/j.jmgm.2026.109280","DOIUrl":"10.1016/j.jmgm.2026.109280","url":null,"abstract":"<div><div>Quantitative structure property relationship(QSPR) has emerged as an indispensable tool for the estimation of physicochemical properties in drug molecules using mathematical and computational methods. Here, we introduce novel reverse degree based topological indices to see their applicability in case of selected antibiotic compounds property prediction. Reliable models to predict properties such as the boiling point, molar refractivity and enthalpy of vaporization exist to correlate molecular structure with experimentally reported physicochemical parameters. We have analyzed structurally different antibiotics with regression models developed in Python and SPSS in order to guarantee the robustness and reproducibility. We note here that predictive measures of cubic regression models seem to perform better, as observed through generally greater correlation coefficients. The results show that the reverse topological indices are efficient for recording structural differences in antibiotic molecules and they can be excellent descriptors for predicting their physical and chemical properties. It also stresses that, the use of reverse degree based descriptors on antibiotic compounds is new, providing a basis for further QSPR modeling for more general drug families. This work is part of a growing trend to study the interfaces between graph theory and cheminformatics where new indices help to improve our understanding over molecular properties with importance for drug design.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"144 ","pages":"Article 109280"},"PeriodicalIF":3.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145980543","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}