Journal of molecular graphics & modelling最新文献

{"title":"Unveiling charge transfer kinetics and static-dynamic nonlinear optical switching in 2-phenylthiophene push-pull chromophores: DFT-based theoretical modelling for enhanced harmonic generation and electro-optic applications","authors":"Sehar Nadeem ,&nbsp;Abida Anwar ,&nbsp;Muhammad Usman Khan ,&nbsp;Munazza Idrees ,&nbsp;Mohamed A. El-Tayeb ,&nbsp;Mahmoud A.A. Ibrahim","doi":"10.1016/j.jmgm.2025.109061","DOIUrl":"10.1016/j.jmgm.2025.109061","url":null,"abstract":"<div><div>Addressing the growing demand for ultrafast photonic nonlinear optical (NLO) materials, ultrafast switching NLO behaviour was studied in detail in 2-phenylthiophene-based push-pull chromophores using laser pulses at 532 and 1064 nm. The EOPE β (−ω, ω, 0) and SHG β (−2ω, ω, ω) calculations for these laser pulses demonstrate an incredible NLO response with efficient energetic offsets that are approximately six times larger than BSS-1. Moreover, the correlation between experimental and theoretical dipole moments and UV absorption (λ_(exp) = 397, <em>λ_max</em> = 394.94 nm) is analyzed, emphasizing its impact on developing NLO switching devices. Quantum chemical calculations, such as frontier molecular orbitals (FMOs), UV–Vis investigation, electron-hole overlap analysis, non-covalent interaction (NCI), molecular electrostatic potential (MEP), natural bond orbitals (NBOs), along with static and frequency-dependent NLO were performed to determine the effect of donor and acceptor modification on the enhanced harmonic generation of designed chromophores (BSSR1-BSSR8 and reference BSS-1). Notably, outstanding NLO findings were obtained for nitro and cyano-based acceptor compounds. Interestingly, among all the derivatives, BSSR4 and BSSR5 had the lowest E_gap values of 1.09 and 1.246 eV, respectively, and the E_gap values were found in the following decreasing order: BSS-1 (R) &gt; BSSR1 &gt; BSSR3 &gt; BSSR7 &gt; BSSR6 &gt; BSSR2 &gt; BSSR8 &gt; BSSR5 &gt; BSSR4. Surprisingly, BSSR5 and BSSR4 had maximum NLO (α and β) amplitudes of 8.62 × 10² and 8.09 × 10⁵ a.u in the gas phase, respectively, indicating their potential towards all-optical computing and ultrahigh bandwidth information processing. These findings underscore the significance of charge transfer dynamics and ultrafast NLO switching in 2-phenylthiophene push-pull chromophores, paving the way for advanced harmonic generation and cutting-edge electro-optic applications.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"139 ","pages":"Article 109061"},"PeriodicalIF":2.7,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143886424","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":"Fine-tuning property domain weighting factors and the objective function in force-field parameter optimization","authors":"Robin Strickstrock ,&nbsp;Alexander Hagg ,&nbsp;Marco Hülsmann ,&nbsp;Karl N. Kirschner ,&nbsp;Dirk Reith","doi":"10.1016/j.jmgm.2025.109035","DOIUrl":"10.1016/j.jmgm.2025.109035","url":null,"abstract":"<div><div>Force field (FF) based molecular modeling is an often used method to investigate and study structural and dynamic properties of (bio-)chemical substances and systems. When such a system is modeled or refined, the force-field parameters need to be adjusted. This force-field parameter optimization can be a tedious task and is always a trade-off in terms of errors regarding the targeted properties. To better control the balance of various properties’ errors, in this study we introduce weighting factors for the optimization objectives. Different weighting strategies are compared to fine-tune the balance between bulk-phase density and relative conformational energies (RCE), using <span><math><mi>n</mi></math></span>-octane as a representative system. Additionally, a non-linear projection of the individual property-specific parts of the optimized loss function is deployed to further improve the balance between them. The results show that the combined error for the reproduction of the properties targeted in this optimization is reduced. Furthermore, the transferability of the force field parameters (FFParams) to chemically similar systems is increased. One interesting outcome is a large variety in the resulting optimized FFParams and corresponding errors, suggesting that the optimization landscape is multi-modal and very dependent on the weighting factor setup. We conclude that adjusting the weighting factors can be a very important feature to lower the overall error in the FF optimization procedure, giving researchers the possibility to fine-tune their FFs.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"139 ","pages":"Article 109035"},"PeriodicalIF":2.7,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143876647","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 monomeric chorismate mutase shows large reduction in conformational diversity of loops upon binding of the transition state analog","authors":"Farindra Kumar Mahto ,&nbsp;Iqra Hamid ,&nbsp;Swati Bhattacharya","doi":"10.1016/j.jmgm.2025.109059","DOIUrl":"10.1016/j.jmgm.2025.109059","url":null,"abstract":"<div><div>In this <em>in silico</em> study, we investigated the structure and dynamics of the molten globule enzyme, monomeric chorismate mutase, which catalyzes the conversion of chorismate to prephenate despite its molten globule state. The primary aim was to understand how the enzyme stabilizes the transition state of the reaction while maintaining its molten globule characteristics. Using the transition state analog (TSA) from the NMR structure (PDB code 2GTV), molecular dynamics simulations revealed multiple hydrogen bonds between three of the enzyme's helices and the TSA. Specific residues that formed stable hydrogen bonds with the TSA were identified as potential mutation targets. Furthermore, the binding of the TSA significantly reduced the entropy of the enzyme and led to the rigidification of the backbone dihedrals across all helices. The flexibility of the loop connecting helices 1 and 2, was also analyzed, showing reduced conformational diversity upon TSA binding. Structural differences between the apo and TSA-bound forms were noted, with helices 3 and 4 exhibiting altered helicity, including a kink in helix 3 and unravelling in helix 4. Despite its molten globule nature, monomeric chorismate mutase can stabilize the TSA through hydrogen bonds involving charged residues, which are essential for maintaining the helix bundle structure. This study highlights the importance of local structural dynamics and entropy changes in enzyme catalysis, offering insights into how molten globule states can support efficient enzymatic activity.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"138 ","pages":"Article 109059"},"PeriodicalIF":2.7,"publicationDate":"2025-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143864715","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 structures, bonding, energetics and interactions of aqua complexes of actinide ions at various oxidation states using density functional theory","authors":"Priya Yadav ,&nbsp;Niharendu Choudhury ,&nbsp;Dilip K. Maity","doi":"10.1016/j.jmgm.2025.109057","DOIUrl":"10.1016/j.jmgm.2025.109057","url":null,"abstract":"<div><div>A systematic study of interactions of U, Np and Pu ions with water in their all possible oxidation states (OSs) has been performed using DFT with triple zeta basis sets, hybrid functional and D3 dispersion correction. In gaseous phase, the maximum coordination of 9 water molecules is observed for U in both +3 and + 4 OSs and Np in +4 OS, whereas the same of 10 water molecules is obtained in +3 OS of Np and both +3 and + 4 OSs of Pu. However, in +5 and + 6 OSs, the actinide oxy ions are solvated by maximum 5 water molecules for all the three actinides, whereas in +7 state of both Np and Pu, there are 4 water molecules. Application of COSMO solvation model, although changes binding energy significantly, but does not change the maximum coordination number of all the complexes except for Np⁴⁺, in which the maximum coordination number changes from 9 to 10. However, the most favourable coordination number calculated using step-wise hydration energy in cases of complexes in gaseous phase and COSMO bulk phase is quite different. The calculated negative binding energies with the non-negative vibrational frequencies of the optimized complexes signify true minimum energy structures. The stretching frequencies of the actinide-oxygen (Ac=O) double bonds decrease whereas those of water O-H bonds (of water ligand) increase as the number of water molecules in the first solvation shell of the ions increases. One of the major highlights of the present investigation is the use of non-covalent interaction (NCI) and reduced density gradient (RDG) methods to reveal the importance of small but significant weak interactions like van der Waals, dipole-dipole and steric repulsion in stabilizing these complexes. Present study provides a comprehensive systematic analysis of structure, bonding, energetics and interaction of aqua complexes of three actinides in their all available oxidation states by treating all these complexes at the same level of theory.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"139 ","pages":"Article 109057"},"PeriodicalIF":2.7,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143882045","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":"Protein recognition is chiefly mediated by the CDR2 region in TREM2 - an in silico characterization","authors":"Pedro H.S. Dantas ,&nbsp;Amanda O. Matos ,&nbsp;Mike T.C. Colmenares ,&nbsp;Vinícius A.F. Costa ,&nbsp;Andrei G. Felice ,&nbsp;José R.C. Neto ,&nbsp;Siomar C. Soares ,&nbsp;Marcelle Silva-Sales ,&nbsp;Bruno J. Neves ,&nbsp;Helioswilton Sales-Campos","doi":"10.1016/j.jmgm.2025.109058","DOIUrl":"10.1016/j.jmgm.2025.109058","url":null,"abstract":"<div><div>The Triggering Receptor Expressed on Myeloid cells 2 (TREM2) is an immune receptor with three complementarity-determining regions (CDR1-3) that primarily interact with the receptor's ligands. Aside from its role in reducing inflammation, enhancing phagocytosis, and contributing to cellular maturation and survival, TREM2 also contributes to the pathophysiology of neurodegenerative disorders, cancer, and metabolic diseases. Therefore, understanding how the receptor interacts with its ligands is essential to mitigate its adverse effects and/or to foster the development of new therapeutic approaches. Thus, our research focused on understanding the interactions between TREM2 and its protein ligands: APOA1, APOA2, APOE3, APOE4, APOJ, C1q, Galectin-3, cyclophilin A, Heat shock protein 60 (HSP60), IL-34, IL-4, the SARS-CoV-2 membrane protein and the cholera toxin subunit B, TDP-43 using <em>in silico</em> methods, such as molecular docking and molecular dynamics simulations. TREM2 showed a higher affinity and stability with HSP60, APOA2, Cyclophilin A, Galectin-3, TDP-43 and C1q when compared to the other protein ligands. Notably, our data suggest that TREM2 interacts with its ligands predominantly through the CDR2 region by the following residues: N68, L69, W70, L71, L72, F74 and R76. Our findings indicate that the CDR2 region can be a crucial target for the development of inhibitory or agonistic approaches targeting the receptor's activity.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"138 ","pages":"Article 109058"},"PeriodicalIF":2.7,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143869022","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 ankyrin repeat proteins that bind to the insulin-like growth factor type 1 receptor","authors":"José Daniel Mahecha-Ortíz ,&nbsp;Sergio Enríquez-Flores ,&nbsp;Ignacio De la Mora De la Mora ,&nbsp;Luis A. Flores-López ,&nbsp;Pedro Gutierrez-Castrellón ,&nbsp;Gabriel López-Velázquez ,&nbsp;Ruth Sánchez-Mora ,&nbsp;Itzhel García-Torres","doi":"10.1016/j.jmgm.2025.109055","DOIUrl":"10.1016/j.jmgm.2025.109055","url":null,"abstract":"<div><div>Ankyrins are proteins widely distributed in nature that mediate protein‒protein interactions. Owing to their outstanding stability and ability to recognize targets, ankyrins have been used as therapeutic and diagnostic tools in several diseases, including cancer. Insulin-like growth factor type 1 receptor (IGF-1R) is overexpressed in a variety of cancers, making it an attractive molecular target<strong>.</strong> Advances in anticancer treatment have focused on inhibiting the binding between IGF-1R and its natural ligand, IGF1. In this work, three ankyrins were designed to interact with IGF-1R, and molecular models using AlphaFold were generated. The designed ankyrin sequences included amino acids of IGF1 that recognize IGF-1R: a two-module ankyrin (DAN2SON), a loop ankyrin (Loop-DAN2SON) and a bispecific ankyrin (BI-DAN2SON-D1). Models with the best results from the predicted local distance difference test and predicted assigned error values were used to perform rigid binding tests with the ClusPro server. The best complexes were selected based on the binding energies. Further analysis of the interactions was performed with the PDBsum server. The three IGF1-R complexes showed negative free binding energies, indicating that the binding of these proteins could be energetically favorable. Molecular binding assays revealed that DAN2SON and Loop-DAN2SON bind to IGF-1R at the natural ligand binding site via hydrogen bonds and salt bridge interactions. This work shows that using artificial intelligence to generate protein models allows prediction of interactions between ankyrins and the IGF-1R, to be confirmed in subsequent studies using both in <em>vitro</em> and <em>in vivo</em> models.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"139 ","pages":"Article 109055"},"PeriodicalIF":2.7,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143873802","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":"How a mixture of urinary human serum albumin fragments survives in urine-mimicking pH conditions: Simulation studies","authors":"Chanya Archapraditkul ,&nbsp;Deanpen Japrung ,&nbsp;Prapasiri Pongprayoon","doi":"10.1016/j.jmgm.2025.109051","DOIUrl":"10.1016/j.jmgm.2025.109051","url":null,"abstract":"<div><div>One of effective indicators for screening and tracking kidney and diabetic disorders is the microalbuminuria level. The fresh urine is required for effectively measuring a microalbuminuria level. The presence of urinary proteases leads to the albumin fragmentation which can interfere the results. Some albumin fragments are reported to be potential clinical biomarkers where their chemistry in urine is incompletely understood. This information is crucial for the effective detection of urinary albumin fragments. Recently, nine fragmented albumins (F1-F9) were identified in urine where no structural and dynamic information is available. Thus, in this work, the structural and dynamic properties of the F1-F9 aqueous mixture at urine pHs (pH 4.5, 7, and 8) are studied. Molecular Dynamics (MD) simulations are performed to understand the behaviour of fragmented albumin mixture in a molecular level. The spontaneous fragment aggregation is captured at all pHs where the complete aggregation is only found at pH 7 and 8. No specific aggregation mechanism is identified. The formation of fragment aggregate is driven by electrostatic interactions. Most fragments are unfolded. F8 is found to be the most stable fragment. F8 and other fragments are suggested to be potential disease biomarkers. The fragment aggregation found here can thus reduce the detection efficacy of urinary albumin fragments in a sample. The knowledge obtained here will be useful for urinary albumin detection, sample stability, and proteomic analysis of urine.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"138 ","pages":"Article 109051"},"PeriodicalIF":2.7,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143860574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DFT insights into assembling [8]MCPP with [14]pyridine nanobelts for amino acid sensing","authors":"Ahmad Khaleel AlOmari","doi":"10.1016/j.jmgm.2025.109056","DOIUrl":"10.1016/j.jmgm.2025.109056","url":null,"abstract":"<div><div>The progress in designing nanoscale electronic sensors for detecting amino acids (AAs) has attracted considerable interest due to their ability to enable label-free and real-time detection. In this study, the [14]pyridine@[8]MCPP system formed by assembling [8]cycloparaphenylene ([8]MCPP) with [14]pyridine methylene-bridged nanobelts was investigated using density functional theory (DFT) calculations as a potential sensor for five amino acids: glycine (Gly), alanine (Ala), threonine (Thr), leucine (Leu), and aspartic acid (Asp). The sensing capabilities of the assembled structure were evaluated through various analyses, including frontier molecular orbital (FMO), density of states (DOS), quantum theory of atoms in molecules (QTAIM), non-covalent interactions (NCI), and electron density difference (EDD). The energy gap of the [14]pyridine@[8]MCPP assembly was influenced by the presence of amino acids, with the most significant change (−8.75 %) observed in the [14]pyridine@[8]MCPP/Asp complex. Furthermore, QTAIM and NCI analyses indicated that the interactions between AAs and the [14]pyridine@[8]MCPP assembly are primarily governed by van der Waals (vdW) forces. The short recovery times (3.47 × 10⁻¹⁰ to 1.27 × 10⁻⁶ s) and favorable sensor responses (0.09–0.17) of the [14]pyridine@[8]MCPP/AA complexes at 298 K suggest that this assembly could serve as an effective material for detecting amino acids. These findings underscore the potential of assembled nanostructures as valuable candidates for amino acid sensing applications.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"138 ","pages":"Article 109056"},"PeriodicalIF":2.7,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143864716","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":"Interpretable machine learning and graph attention network based model for predicting PAMPA permeability","authors":"Upashya Parasar ,&nbsp;Orchid Baruah ,&nbsp;Debasish Saikia ,&nbsp;Pankaj Bharali ,&nbsp;Hridoy Jyoti Mahanta","doi":"10.1016/j.jmgm.2025.109050","DOIUrl":"10.1016/j.jmgm.2025.109050","url":null,"abstract":"<div><div>Parallel artificial membrane permeability assay (PAMPA) is widely used in the early phases of drug discovery as it is quite robust and offers high throughput. It serves as a platform for assessing the permeability and absorption of pharmaceutical compounds across lipid membranes. This study uses machine learning (Random forest or RF, Explainable boosting machine or EBM and Adaboost) and deep learning (Graph attention network or GAT) to build models to predict PAMPA permeability. A curated dataset of 5447 compounds with PAMPA permeability scores (in a scale 10⁻⁶ cm/s) was used to train and validate these models. During validation it was observed that, RF and EBM models could predict with an accuracy of 81 % and 80 % respectively, whereas with Adaboost and GAT, the accuracies were limited 76 % and 74 % respectively. Further, an external dataset was used to screen the predictive capability of these models and results showed that RF, EBM and Adaboost had quite similar accuracies with 91 %, 90 % and 89 % respectively. Interestingly, with this external dataset, the GAT-based model also reached a significant accuracy of 86 %. The overall results show that all the models in this study could well predict PAMPA permeability over the benchmark and covering diverse chemical space. All the datasets and codes for developing these models have been deposited on the GitHub platform (<span><span>https://github.com/hridoy69/pampa_premeability</span><svg><path></path></svg></span>).</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"138 ","pages":"Article 109050"},"PeriodicalIF":2.7,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143833245","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 inhibitors targeting EGFR L858R/T790M/C797S against NSCLC by molecular docking, MD simulation, and DFT approaches","authors":"Chaochun Wei ,&nbsp;Cuicui Ji ,&nbsp;Keli Zong ,&nbsp;Xiaokun Zhang ,&nbsp;Qidi Zhong ,&nbsp;Hong Yan ,&nbsp;Juan Wang","doi":"10.1016/j.jmgm.2025.109052","DOIUrl":"10.1016/j.jmgm.2025.109052","url":null,"abstract":"<div><div>The resistance of growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in non-small cell lung cancer (NSCLC), especially against the EGFR L858R/T790M/C797S mutations, remains an ongoing challenge. In this study, we screened a total of 2.05 million compounds from the ChEMBL database through virtual screening, identifying five promising candidates with high binding affinities and favourable ADMET properties. These candidates were further evaluated through molecular dynamics (MD) simulations, revealing more restricted conformational changes and enhanced stability compared to <strong>Osimertinib</strong>. Protein-ligand interaction analyses highlighted a broader range of stabilizing interactions in the binding domain. Additionally, the binding free energies of the compounds showed that compounds <strong>1</strong>–<strong>5</strong> ranged from −34.95 to −45.54 kcal/mol, which were lower compared to <strong>Osimertinib</strong> (−34.49 kcal/mol), suggesting a stronger binding affinity. Subsequently, density functional theory (DFT) calculations provided further insights into the electronic properties of the compounds, which were essential for understanding the compounds' reactivity and potential interactions with the target protein. In conclusion, the five identified compounds exhibit promising drug-like properties and may serve as lead candidates for the development of new treatments targeting EGFR L858R/T790M/C797S resistance mutations in NSCLC.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"138 ","pages":"Article 109052"},"PeriodicalIF":2.7,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143829634","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}