Pub Date : 2025-11-01DOI: 10.1016/j.jmgm.2025.109205
Shanza Hameed , Shaukat Ali , Ijaz Ahmad Bhatti , Muhammad Yasin Naz
Flexible perovskite solar cells (PSCs) are emerging as a promising photovoltaic technology for portable and wearable electronics, offering excellent power conversion efficiencies (PCEs) and ease of processing. In this work, we present five newly designed foldable hole transport materials (HTMs), labeled C1M1-C1M5, engineered by thiophene-bridged acceptor modifications of the reference CM molecule. Using density functional theory (DFT), we explore the structural, electronic, optical, and photovoltaic properties of these molecules.
The results show that the newly designed HTMs exhibit narrow band gaps (1.65–2.32 eV), significantly lower than the CM reference (3.75 eV). Notably, the extended conjugation length of the molecules contributes to their red-shifted absorption (up to 832 nm), enhanced dipole moments (ranging from 6.37 to 19.14 D), and improved exciton dissociation, particularly for C1M5, with an exciton binding energy of 0.22 eV. Furthermore, the charge transport characteristics were found to be promising, with C1M4 exhibiting the highest charge transmission (λe = 0.036577, λh = 0.050162), where electron transport was slightly more favorable than hole transport. In conclusion, these newly engineered HTMs are highly promising for next-generation solar devices due to their excellent solution processability, efficient light harvesting, and charge transport capabilities.
{"title":"Design and evaluation of hole transporting molecules for flexible perovskite solar cells: Enhancing efficiency and optoelectronic properties","authors":"Shanza Hameed , Shaukat Ali , Ijaz Ahmad Bhatti , Muhammad Yasin Naz","doi":"10.1016/j.jmgm.2025.109205","DOIUrl":"10.1016/j.jmgm.2025.109205","url":null,"abstract":"<div><div>Flexible perovskite solar cells (PSCs) are emerging as a promising photovoltaic technology for portable and wearable electronics, offering excellent power conversion efficiencies (PCEs) and ease of processing. In this work, we present five newly designed foldable hole transport materials (HTMs), labeled C1M1-C1M5, engineered by thiophene-bridged acceptor modifications of the reference CM molecule. Using density functional theory (DFT), we explore the structural, electronic, optical, and photovoltaic properties of these molecules.</div><div>The results show that the newly designed HTMs exhibit narrow band gaps (1.65–2.32 eV), significantly lower than the CM reference (3.75 eV). Notably, the extended conjugation length of the molecules contributes to their red-shifted absorption (up to 832 nm), enhanced dipole moments (ranging from 6.37 to 19.14 D), and improved exciton dissociation, particularly for C1M5, with an exciton binding energy of 0.22 eV. Furthermore, the charge transport characteristics were found to be promising, with C1M4 exhibiting the highest charge transmission (λe = 0.036577, λh = 0.050162), where electron transport was slightly more favorable than hole transport. In conclusion, these newly engineered HTMs are highly promising for next-generation solar devices due to their excellent solution processability, efficient light harvesting, and charge transport capabilities.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"142 ","pages":"Article 109205"},"PeriodicalIF":3.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145444880","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}
Pub Date : 2025-11-01Epub Date: 2025-08-06DOI: 10.1016/j.jmgm.2025.109135
S Rehan Ahmad, Md Zeyaullah, Yousef Zahrani, Mohammad Suhail Khan, Khursheed Muzammil, Adam Dawria
Neurodegenerative tauopathies, such as Alzheimer's disease, are closely associated with the dysregulation of tau phosphorylation, a process regulated in part by the serine/threonine kinase MARK4. In this study, we explored phytochemicals derived from Bacopa monnieri as potential natural inhibitors of MARK4. Using pressurized liquid extraction with an ethanol-water mixture, we efficiently extracted bioactive compounds from Bacopa leaves. LC-MS analysis identified 25 distinct phytoconstituents spanning flavonoids, triterpenoids, cucurbitacins, sterols, and alkaloids. In silico analysis revealed that several compounds, including oroxindin, cucurbitacin B, and bacosine, bind strongly to the catalytic pocket of MARK4. Molecular dynamics simulations confirmed their stability within the MARK4 active site, with oroxindin demonstrating the most favorable thermodynamic and conformational profile. Principal component and free energy landscape analyses further supported their capacity to stabilize MARK4 in low-energy conformations. Microscale thermophoresis further validated high-affinity binding of MARK4 with oroxindin, while other four compounds also show strong interaction with MARK4. MTT assays in SH-SY5Y cells confirmed the non-cytotoxic nature of all five lead compounds across a concentration range of 10 nM to 10 μM. Cellular assays revealed a significant reduction in Tau-GFP aggregates upon treatment with the compounds, particularly oroxindin. These results highlight oroxindin and other Bacopa monnieri phytochemicals as promising natural inhibitors of MARK4, with potential to attenuate tau pathology in neurodegenerative diseases.
{"title":"Phytochemicals from Bacopa monnieri as small molecule modulators of MARK4: A multi-modal strategy for preventing Alzheimer's disease-causing tau aggregation.","authors":"S Rehan Ahmad, Md Zeyaullah, Yousef Zahrani, Mohammad Suhail Khan, Khursheed Muzammil, Adam Dawria","doi":"10.1016/j.jmgm.2025.109135","DOIUrl":"10.1016/j.jmgm.2025.109135","url":null,"abstract":"<p><p>Neurodegenerative tauopathies, such as Alzheimer's disease, are closely associated with the dysregulation of tau phosphorylation, a process regulated in part by the serine/threonine kinase MARK4. In this study, we explored phytochemicals derived from Bacopa monnieri as potential natural inhibitors of MARK4. Using pressurized liquid extraction with an ethanol-water mixture, we efficiently extracted bioactive compounds from Bacopa leaves. LC-MS analysis identified 25 distinct phytoconstituents spanning flavonoids, triterpenoids, cucurbitacins, sterols, and alkaloids. In silico analysis revealed that several compounds, including oroxindin, cucurbitacin B, and bacosine, bind strongly to the catalytic pocket of MARK4. Molecular dynamics simulations confirmed their stability within the MARK4 active site, with oroxindin demonstrating the most favorable thermodynamic and conformational profile. Principal component and free energy landscape analyses further supported their capacity to stabilize MARK4 in low-energy conformations. Microscale thermophoresis further validated high-affinity binding of MARK4 with oroxindin, while other four compounds also show strong interaction with MARK4. MTT assays in SH-SY5Y cells confirmed the non-cytotoxic nature of all five lead compounds across a concentration range of 10 nM to 10 μM. Cellular assays revealed a significant reduction in Tau-GFP aggregates upon treatment with the compounds, particularly oroxindin. These results highlight oroxindin and other Bacopa monnieri phytochemicals as promising natural inhibitors of MARK4, with potential to attenuate tau pathology in neurodegenerative diseases.</p>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"140 ","pages":"109135"},"PeriodicalIF":3.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144799376","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}
Pub Date : 2025-11-01DOI: 10.1016/j.jmgm.2025.109211
Alexei Iakhiaev
The unbinding of the Vorapaxar (VPX) from the β-sheet of the Endothelial cell Protein C Receptor (EPCR) can be observed during a 100 ns unbiased Molecular Dynamics simulation while VPX in the hydrophobic cleft remained in a bound state during a microsecond-long simulation. Three sites of VPX participate in binding to the EPCR: the carbamic acid tail, the central naphthol-furan group, and the fluoro-phenyl tail. Empirical Mode Decomposition of the EPCR-VPX interface distances in the trajectories revealed a resonant increase in the vibration amplitudes for the frequency range of 1–10 GHz associated with the unbinding of the VPX sites from β-sheet of EPCR. The VPX molecule in the hydrophobic cleft experienced occasional reorientations without unbinding. The main difference between the two VPX-binding sites of EPCR was the direction of the ligand vibrations relative to the ligand escape route: collinear for the β-sheet and perpendicular to the escape direction for cleft-bound VPX. The observed residence times of VPX bound to the β-sheet were 1–10 ns at 10 °C and more than 100 ns at 37 °C for soluble EPCR. The residence time was 1–10 ns for both temperatures for full-length EPCR (mEPCR). The resonant conditions for soluble EPCR were achieved by reducing the thermal noise, suggesting the involvement of stochastic resonance. The mEPCR, which has lower frequencies of normal modes than sEPCR, could afford the resonant conditions for both temperatures. Thus, ligand unbinding in the EPCR-VPX model was triggered by enhanced vibrations induced by the stochastic resonance.
{"title":"Stochastic resonance represents one of the mechanisms that trigger protein ligand unbinding","authors":"Alexei Iakhiaev","doi":"10.1016/j.jmgm.2025.109211","DOIUrl":"10.1016/j.jmgm.2025.109211","url":null,"abstract":"<div><div>The unbinding of the Vorapaxar (VPX) from the β-sheet of the Endothelial cell Protein C Receptor (EPCR) can be observed during a 100 ns unbiased Molecular Dynamics simulation while VPX in the hydrophobic cleft remained in a bound state during a microsecond-long simulation. Three sites of VPX participate in binding to the EPCR: the carbamic acid tail, the central naphthol-furan group, and the fluoro-phenyl tail. Empirical Mode Decomposition of the EPCR-VPX interface distances in the trajectories revealed a resonant increase in the vibration amplitudes for the frequency range of 1–10 GHz associated with the unbinding of the VPX sites from β-sheet of EPCR. The VPX molecule in the hydrophobic cleft experienced occasional reorientations without unbinding. The main difference between the two VPX-binding sites of EPCR was the direction of the ligand vibrations relative to the ligand escape route: collinear for the β-sheet and perpendicular to the escape direction for cleft-bound VPX. The observed residence times of VPX bound to the β-sheet were 1–10 ns at 10 °C and more than 100 ns at 37 °C for soluble EPCR. The residence time was 1–10 ns for both temperatures for full-length EPCR (mEPCR). The resonant conditions for soluble EPCR were achieved by reducing the thermal noise, suggesting the involvement of stochastic resonance. The mEPCR, which has lower frequencies of normal modes than sEPCR, could afford the resonant conditions for both temperatures. Thus, ligand unbinding in the EPCR-VPX model was triggered by enhanced vibrations induced by the stochastic resonance.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"142 ","pages":"Article 109211"},"PeriodicalIF":3.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145459038","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}
Pub Date : 2025-11-01DOI: 10.1016/j.jmgm.2025.109206
Norma Flores-Holguín , Juan Frau , Daniel Glossman-Mitnik
Advanced Glycation Endproducts (AGEs) are toxic compounds formed through non-enzymatic glycation processes, and they are strongly implicated in diabetes, neurodegeneration, cardiovascular disease, and aging. Their accumulation alters biomolecular structure and function, making the inhibition of AGE formation a relevant therapeutic strategy. This review highlights computational approaches applied to amino acids and peptides as AGE inhibitors: Conceptual Density Functional Theory (CDFT) for global and local reactivity analysis, molecular docking and molecular dynamics for binding and stability assessments, and QSAR/machine learning methods for large-scale screening. These integrated strategies support the rational design of peptide-based AGE inhibitors and outlines future directions for therapeutic development.
{"title":"Computational strategies for exploring amino acids and peptides as inhibitors of Advanced Glycation Endproducts","authors":"Norma Flores-Holguín , Juan Frau , Daniel Glossman-Mitnik","doi":"10.1016/j.jmgm.2025.109206","DOIUrl":"10.1016/j.jmgm.2025.109206","url":null,"abstract":"<div><div>Advanced Glycation Endproducts (AGEs) are toxic compounds formed through non-enzymatic glycation processes, and they are strongly implicated in diabetes, neurodegeneration, cardiovascular disease, and aging. Their accumulation alters biomolecular structure and function, making the inhibition of AGE formation a relevant therapeutic strategy. This review highlights computational approaches applied to amino acids and peptides as AGE inhibitors: Conceptual Density Functional Theory (CDFT) for global and local reactivity analysis, molecular docking and molecular dynamics for binding and stability assessments, and QSAR/machine learning methods for large-scale screening. These integrated strategies support the rational design of peptide-based AGE inhibitors and outlines future directions for therapeutic development.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"142 ","pages":"Article 109206"},"PeriodicalIF":3.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145437670","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}
Pub Date : 2025-11-01Epub Date: 2025-08-06DOI: 10.1016/j.jmgm.2025.109136
Nahed H Teleb, Yasmeen G Abou El-Reash, Nuha Y Elamin, Mahmoud A S Sakr, Mohamed A Saad, Hazem Abdelsalam
The electrochemical nitrogen reduction reaction (N2RR) offers a sustainable route to ammonia production under ambient conditions but remains limited by inert N ≡ N bond activation and competitive hydrogen evolution reaction (HER). Herein, we employ first-principles density functional theory (DFT) to systematically investigate the N2RR activity of graphyne (GY) doped with single-atom transition metals (Fe, Mo, Ru, W). Structural analysis reveals strong binding and minimal distortion of the TM dopants on the porous, π-conjugated GY scaffold, with Fe-GY and W-GY exhibiting the highest stability. TM doping induces substantial bandgap narrowing and introduces localized d-orbital states near the Fermi level, enhancing charge transfer and catalytic potential. Adsorption studies show that TM sites effectively activate N2 via π-backdonation, with W-GY inducing the greatest N ≡ N bond elongation. Free energy profiles demonstrate that TM-GY catalysts significantly lower the limiting potential for N2RR compared to pristine GY, with Fe-Gy and W-GY achieving the most favorable limiting potential via the alternating mechanism. HER analysis reveals Ru-GY possesses near-optimal hydrogen adsorption energy (ΔGH = -0.25 eV), suggesting high activity but possible competition with N2RR. In contrast, Mo-GY and W-GY exhibit stronger H binding, potentially suppressing HER and improving N2RR selectivity. This work identifies TM-doped GY as a versatile platform for single-atom catalysis and offers design principles for optimizing selectivity and efficiency in electrochemical nitrogen fixation.
{"title":"Engineering graphyne-supported single-atom catalysts for efficient nitrogen reduction to ammonia: First-principles investigation.","authors":"Nahed H Teleb, Yasmeen G Abou El-Reash, Nuha Y Elamin, Mahmoud A S Sakr, Mohamed A Saad, Hazem Abdelsalam","doi":"10.1016/j.jmgm.2025.109136","DOIUrl":"10.1016/j.jmgm.2025.109136","url":null,"abstract":"<p><p>The electrochemical nitrogen reduction reaction (N<sub>2</sub>RR) offers a sustainable route to ammonia production under ambient conditions but remains limited by inert N ≡ N bond activation and competitive hydrogen evolution reaction (HER). Herein, we employ first-principles density functional theory (DFT) to systematically investigate the N<sub>2</sub>RR activity of graphyne (GY) doped with single-atom transition metals (Fe, Mo, Ru, W). Structural analysis reveals strong binding and minimal distortion of the TM dopants on the porous, π-conjugated GY scaffold, with Fe-GY and W-GY exhibiting the highest stability. TM doping induces substantial bandgap narrowing and introduces localized d-orbital states near the Fermi level, enhancing charge transfer and catalytic potential. Adsorption studies show that TM sites effectively activate N<sub>2</sub> via π-backdonation, with W-GY inducing the greatest N ≡ N bond elongation. Free energy profiles demonstrate that TM-GY catalysts significantly lower the limiting potential for N<sub>2</sub>RR compared to pristine GY, with Fe-Gy and W-GY achieving the most favorable limiting potential via the alternating mechanism. HER analysis reveals Ru-GY possesses near-optimal hydrogen adsorption energy (ΔG<sub>H</sub> = -0.25 eV), suggesting high activity but possible competition with N<sub>2</sub>RR. In contrast, Mo-GY and W-GY exhibit stronger H binding, potentially suppressing HER and improving N<sub>2</sub>RR selectivity. This work identifies TM-doped GY as a versatile platform for single-atom catalysis and offers design principles for optimizing selectivity and efficiency in electrochemical nitrogen fixation.</p>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"140 ","pages":"109136"},"PeriodicalIF":3.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144804180","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}
The fibroblast growth factor receptor 1 (FGFR1) plays a crucial role in cancer development and progression, primarily through mechanisms involving carcinogenesis and angiogenesis. Aberrant FGFR1 signalling has been implicated in various cancers, including lung, breast, neck and urothelial carcinoma. Despite the recognized oncogenic potential of FGFR1, therapeutic strategies targeting its kinase domain remain inadequately explored. This underscores an urgent need for the development of novel FGFR1 inhibitors, particularly through de novo drug design approaches, to effectively counteract FGFR1-driven malignancies. This research aims to develop novel FGFR1 inhibitors through a multi-step approach involving fragment-based drug design, virtual screening, molecular dynamics simulation (MD) and density functional theory studies (DFT), with the goal of targeting FGFR1's kinase binding domain to inhibit tumor angiogenesis. Initially, known FGFR inhibitor molecules were retrieved and subjected to fragment-based drug designing and virtual screening. Through thorough analysis, molecules containing the pyrido[2,3-d]pyrimidine scaffold were identified as promising candidates. A pyrido[2,3-d]pyrimidine-based database containing 90,952 molecules was subsequently retrieved from PubChem and filtered using molecular docking-based virtual screening resulting 94 molecules having better binding affinity than derazantinib, reference drug. After pharmacokinetic profiling (ADME), and MM-GBSA (Molecular Mechanics-Generalized Born Surface Area) studies, out of 94 molecules only 11 compounds with favorable pharmacokinetic properties and superior MM-GBSA binding free energies were selected. Docking-based screening revealed that selected 11 compounds demonstrated better binding scores than the reference drug, derazantinib. Among them, HIT1, was selected for 150ns molecular dynamics simulation to assess its conformational stability. DFT calculations further confirmed its bio-feasibility by analyzing the HOMO-LUMO energy gap. Overall, the selected lead compounds exhibited enhanced binding affinity, superior conformational stability, favorable pharmacokinetic and pharmacodynamic profiles compared to derazantinib. Present findings suggest that the identified hit molecules hold strong potential for inhibiting FGFR1's kinase domain and disrupting FGFR-associated tumor angiogenesis.
成纤维细胞生长因子受体1 （FGFR1）在癌症的发生和进展中起着至关重要的作用，主要通过涉及致癌和血管生成的机制。异常的FGFR1信号传导与多种癌症有关，包括肺癌、乳腺癌、颈癌和尿路上皮癌。尽管FGFR1具有公认的致癌潜力，但针对其激酶结构域的治疗策略仍未得到充分探索。这强调了迫切需要开发新的FGFR1抑制剂，特别是通过新药物设计方法，以有效对抗FGFR1驱动的恶性肿瘤。本研究旨在通过包括基于片段的药物设计、虚拟筛选、分子动力学模拟（MD）和密度泛函数理论研究（DFT）在内的多步骤方法开发新型FGFR1抑制剂，目标是靶向FGFR1激酶结合结构域抑制肿瘤血管生成。最初，已知的FGFR抑制剂分子被检索并进行基于片段的药物设计和虚拟筛选。通过深入分析，含有吡啶[2,3-d]嘧啶支架的分子被确定为有希望的候选分子。随后从PubChem中检索到一个包含90,952个分子的吡啶[2,3-d]嘧啶数据库，并使用基于分子对接的虚拟筛选进行筛选，得到94个分子的结合亲和力优于对照药物derazantinib。通过药代动力学分析（ADME）和MM-GBSA （Molecular Mechanics-Generalized Born Surface Area）研究，从94个分子中筛选出11个具有良好药代动力学特性和MM-GBSA结合自由能的化合物。基于对接的筛选显示，选定的11种化合物的结合评分优于对照药物derazantinib。其中选择HIT1进行150ns分子动力学模拟，评价其构象稳定性。DFT计算通过分析HOMO-LUMO能隙进一步证实了其生物可行性。总的来说，与derazantinib相比，所选择的先导化合物具有增强的结合亲和力，优越的构象稳定性，良好的药代动力学和药效学特征。目前的研究结果表明，鉴定的撞击分子具有抑制FGFR1激酶结构域和破坏fgfr相关肿瘤血管生成的强大潜力。
{"title":"In silico approaches for the identification of novel FGFR1 inhibitor in cancer: A fragment-based De novo drug designing guided virtual screening approach","authors":"Nidhi Bala , Ashwini Pareek , Agnidipta Das , Bharti Devi , Vinod Kumar , Vikas Jaitak","doi":"10.1016/j.jmgm.2025.109207","DOIUrl":"10.1016/j.jmgm.2025.109207","url":null,"abstract":"<div><div>The fibroblast growth factor receptor 1 (FGFR1) plays a crucial role in cancer development and progression, primarily through mechanisms involving carcinogenesis and angiogenesis. Aberrant FGFR1 signalling has been implicated in various cancers, including lung, breast, neck and urothelial carcinoma. Despite the recognized oncogenic potential of FGFR1, therapeutic strategies targeting its kinase domain remain inadequately explored. This underscores an urgent need for the development of novel FGFR1 inhibitors, particularly through de novo drug design approaches, to effectively counteract FGFR1-driven malignancies. This research aims to develop novel FGFR1 inhibitors through a multi-step approach involving fragment-based drug design, virtual screening, molecular dynamics simulation (MD) and density functional theory studies (DFT), with the goal of targeting FGFR1's kinase binding domain to inhibit tumor angiogenesis. Initially, known FGFR inhibitor molecules were retrieved and subjected to fragment-based drug designing and virtual screening. Through thorough analysis, molecules containing the pyrido[2,3-d]pyrimidine scaffold were identified as promising candidates. A pyrido[2,3-d]pyrimidine-based database containing 90,952 molecules was subsequently retrieved from PubChem and filtered using molecular docking-based virtual screening resulting 94 molecules having better binding affinity than derazantinib, reference drug. After pharmacokinetic profiling (ADME), and MM-GBSA (Molecular Mechanics-Generalized Born Surface Area) studies, out of 94 molecules only 11 compounds with favorable pharmacokinetic properties and superior MM-GBSA binding free energies were selected. Docking-based screening revealed that selected 11 compounds demonstrated better binding scores than the reference drug, derazantinib. Among them, HIT1, was selected for 150ns molecular dynamics simulation to assess its conformational stability. DFT calculations further confirmed its bio-feasibility by analyzing the HOMO-LUMO energy gap. Overall, the selected lead compounds exhibited enhanced binding affinity, superior conformational stability, favorable pharmacokinetic and pharmacodynamic profiles compared to derazantinib. Present findings suggest that the identified hit molecules hold strong potential for inhibiting FGFR1's kinase domain and disrupting FGFR-associated tumor angiogenesis.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"142 ","pages":"Article 109207"},"PeriodicalIF":3.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145444914","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}
Quantitative structure-activity relationship (QSAR) as one of the most important fields of chemometrics provides useful information in pharmaceutical chemistry, drug design, toxicology, and other related areas. In this study, a QSAR model was developed employing image pixels of molecular structure as descriptors to describe the antibacterial activity of pleuromutilin derivatives. Accordingly, a dataset of 54 Pleuromutilin derivatives was collected from the literature, plotted, and transformed into pixels using MATLAB software to generate the desired model. The data were pre-processed through mean-centering and scaling to optimize pixel selection. The suitable descriptors were then extracted using principal component analysis (PCA) and the final model was built followed by partial least squares (PLS) multivariate calibration. The developed QSAR model was validated and novel compounds with antibacterial properties were suggested. In addition, molecular docking studies were utilized to investigate inhibitory activities of proposed new compounds against ribosomal protein (PDB ID: 3G4S). The findings showed high potential of proposed compounds to form strong interactions with key active site residues, confirming their good antibacterial activity and the validity of constructed QSAR model for drug prediction.
{"title":"QSAR study and molecular modeling of pleuromutilin derivatives to predict antibacterial activity: Chemometrics and docking studies","authors":"Masoomeh Naseri , Ali Niazi , Elaheh Omidi , Kowsar Bagherzadeh","doi":"10.1016/j.jmgm.2025.109208","DOIUrl":"10.1016/j.jmgm.2025.109208","url":null,"abstract":"<div><div>Quantitative structure-activity relationship (QSAR) as one of the most important fields of chemometrics provides useful information in pharmaceutical chemistry, drug design, toxicology, and other related areas. In this study, a QSAR model was developed employing image pixels of molecular structure as descriptors to describe the antibacterial activity of pleuromutilin derivatives. Accordingly, a dataset of 54 Pleuromutilin derivatives was collected from the literature, plotted, and transformed into pixels using MATLAB software to generate the desired model. The data were pre-processed through mean-centering and scaling to optimize pixel selection. The suitable descriptors were then extracted using principal component analysis (PCA) and the final model was built followed by partial least squares (PLS) multivariate calibration. The developed QSAR model was validated and novel compounds with antibacterial properties were suggested. In addition, molecular docking studies were utilized to investigate inhibitory activities of proposed new compounds against ribosomal protein (PDB ID: 3G4S). The findings showed high potential of proposed compounds to form strong interactions with key active site residues, confirming their good antibacterial activity and the validity of constructed QSAR model for drug prediction.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"142 ","pages":"Article 109208"},"PeriodicalIF":3.0,"publicationDate":"2025-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145444928","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}
Pub Date : 2025-10-30DOI: 10.1016/j.jmgm.2025.109209
Hadil Faris Alotaibi , Anjan Kumar , Yashwantsinh Jadeja , Suhas Ballal , Shaker Al-Hasnaawei , Abhayveer Singh , T. Krithiga , Subhashree Ray , Kamal Kant Joshi
In recent years, significant attention has been directed toward the application of AuNPs due to their favorable interactions with biological systems and their comparatively low cytotoxicity relative to other metal-based platforms. In this research, we utilize DFT to investigate the interaction between a model Au32NC and tiopronin in both gas and aqueous phases. We present a comprehensive analysis of the structural properties, adsorption energies, and electronic characteristics of the resulting complexes, providing atomic-scale insights into the potential of Au32NCs as nanocarriers drugs. For the Au32NCs, the Lanl2DZ basis set was utilized, while the 6–31++G(d,p) basis set was applied to the tiopronin molecule. The most notable negative adsorption energies are recorded for Au32@ tiopronin, with values of −12.57, −10.38, and −11.16 kcal mol−1 in the gas phase, and −11.54, −7.04, and −3.57 kcal mol−1 in the aqueous environment, respectively. Moreover, AIMD simulations validate the thermal stability of the nanohybrid at 300K, with recovery time identified as a critical factor in drug delivery. The findings indicate that Au32@tiopronin, as a carrier, possesses favorable characteristics from both energetic and structural perspectives, positioning it as a promising candidate for targeted drug delivery applications. This computational study offers valuable insights into the design and development of Au32 nanocarriers for therapeutic agents aimed at assisting rheumatoid arthritis patients in minimizing side effects and enhancing the efficacy of the tiopronin drug.
{"title":"Theoretical assessment of Au32 nanocluster as tiopronin drug agent: DFT calculation and MD simulation; with solvent effect","authors":"Hadil Faris Alotaibi , Anjan Kumar , Yashwantsinh Jadeja , Suhas Ballal , Shaker Al-Hasnaawei , Abhayveer Singh , T. Krithiga , Subhashree Ray , Kamal Kant Joshi","doi":"10.1016/j.jmgm.2025.109209","DOIUrl":"10.1016/j.jmgm.2025.109209","url":null,"abstract":"<div><div>In recent years, significant attention has been directed toward the application of AuNPs due to their favorable interactions with biological systems and their comparatively low cytotoxicity relative to other metal-based platforms. In this research, we utilize DFT to investigate the interaction between a model Au<sub>32</sub>NC and tiopronin in both gas and aqueous phases. We present a comprehensive analysis of the structural properties, adsorption energies, and electronic characteristics of the resulting complexes, providing atomic-scale insights into the potential of Au<sub>32</sub>NCs as nanocarriers drugs. For the Au<sub>32</sub>NCs, the Lanl2DZ basis set was utilized, while the 6–31++G(d,p) basis set was applied to the tiopronin molecule. The most notable negative adsorption energies are recorded for Au<sub>32</sub>@ tiopronin, with values of −12.57, −10.38, and −11.16 kcal mol<sup>−1</sup> in the gas phase, and −11.54, −7.04, and −3.57 kcal mol<sup>−1</sup> in the aqueous environment, respectively. Moreover, AIMD simulations validate the thermal stability of the nanohybrid at 300K, with recovery time identified as a critical factor in drug delivery. The findings indicate that Au32@tiopronin, as a carrier, possesses favorable characteristics from both energetic and structural perspectives, positioning it as a promising candidate for targeted drug delivery applications. This computational study offers valuable insights into the design and development of Au32 nanocarriers for therapeutic agents aimed at assisting rheumatoid arthritis patients in minimizing side effects and enhancing the efficacy of the tiopronin drug.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"142 ","pages":"Article 109209"},"PeriodicalIF":3.0,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145452126","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}
Pub Date : 2025-10-28DOI: 10.1016/j.jmgm.2025.109202
Yunju Zhang , Meilian Zhao , Cen Yao , Yuxi Sun , Huirong Li
In the present investigation, the reaction mechanism and kinetics of the CH2=CHCOOH + O3 reaction are detailed discussed by employing density functional theory (DFT). Both C=C bond cycloaddition and H-abstraction mechanisms were discovered. The computations manifested that the dominant reaction channel is 1,3-dipole cycloaddition reactions of O3 with C=C bond surmounting lower barrier of 3.35 kcal/mol to generate primary ozonide, which dissociated to generate carbonyl oxide known as Criegee diradical intermediate (CIA) and aldehyde. A detailed analysis was conducted on the subsequent reactions of CIs. Research has found that the reaction pathway of new CI containing carboxyl groups with NO, NO2, CH2O, SO2, H2O and O2 is very analogous to that of general CIs. The computed rate constants are agreement with the avaliable experimental data. The atmospheric lifetime is evaluated to be 23.81 days. The rate constants of the generated CIA (O2CHCOOH) with the variety of partners were also computed. Our theoretical computation results may be of great help for further research on atmospheric chemistry of ozone oxidation of unsaturated acids.
{"title":"Theoretical study on the formation of Criegee intermediates from ozonolysis of acrylic acid","authors":"Yunju Zhang , Meilian Zhao , Cen Yao , Yuxi Sun , Huirong Li","doi":"10.1016/j.jmgm.2025.109202","DOIUrl":"10.1016/j.jmgm.2025.109202","url":null,"abstract":"<div><div>In the present investigation, the reaction mechanism and kinetics of the CH<sub>2</sub>=CHCOOH + O<sub>3</sub> reaction are detailed discussed by employing density functional theory (DFT). Both C=C bond cycloaddition and H-abstraction mechanisms were discovered. The computations manifested that the dominant reaction channel is 1,3-dipole cycloaddition reactions of O<sub>3</sub> with C=C bond surmounting lower barrier of 3.35 kcal/mol to generate primary ozonide, which dissociated to generate carbonyl oxide known as Criegee diradical intermediate (CIA) and aldehyde. A detailed analysis was conducted on the subsequent reactions of CIs. Research has found that the reaction pathway of new CI containing carboxyl groups with NO, NO<sub>2</sub>, CH<sub>2</sub>O, SO<sub>2</sub>, H<sub>2</sub>O and O<sub>2</sub> is very analogous to that of general CIs. The computed rate constants are agreement with the avaliable experimental data. The atmospheric lifetime is evaluated to be 23.81 days. The rate constants of the generated CIA (O<sub>2</sub>CHCOOH) with the variety of partners were also computed. Our theoretical computation results may be of great help for further research on atmospheric chemistry of ozone oxidation of unsaturated acids.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"142 ","pages":"Article 109202"},"PeriodicalIF":3.0,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145482126","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}
Pub Date : 2025-10-27DOI: 10.1016/j.jmgm.2025.109203
Khawar Ismail , Ali B.M. Ali , Fakhra Ghafoor , Abhinav Kumar , Dhouha Choukaier , Ghulam Murtaza , Munawar Ali , Ankit D. Oza
In this research work, the double perovskite Cs2AuXY6 (X = Sb, Bi; Y = Cl, Br) is explored as an absorber material in perovskite solar cells (PSCs). Computational simulations were performed by using Generalised Gradient Approximation along with Perdew–Burke–Ernzerhof (GGA-PBE) and modified Becke–Johnson (mBJ) exchange-correlation potential within the WIEN2K software to study the physical properties of Cs2AuXY6. Studied compounds have a cubic crystal structure with space group Fm3m (No 225). Electronic bandgap values for Cs2AuBiCl6, Cs2AuSbCl6 are 0.61, 0.24. Cs2AuBiBr6 is a semimetal (considering GGA-PBE) and has band gaps of 1.62, 1.12, and 0.59 eV (with mBJ), which are very close to the required band gap for solar cell applications according to the Shockley–Queisser limit. In addition to the above, the Optical result shows higher absorption and optical conductivity with minimal reflection in the visible and infrared regions, making them good absorbent materials for PSC. Moreover, the temperature-dependent thermoelectric nature of these compounds was explored by the BoltzTraP code, and the mechanical elastic constants were investigated by the charpin method, which follows the Born stability condition. Therefore, Cs2AuXY6-based PSCs are considered potential materials for charge transport layers, perovskite absorber layers, and conventional halide perovskite compounds.
{"title":"Electronic, optical and thermoelectric performance of Cs2AuXY6 for photovoltaic applications: by DFT method","authors":"Khawar Ismail , Ali B.M. Ali , Fakhra Ghafoor , Abhinav Kumar , Dhouha Choukaier , Ghulam Murtaza , Munawar Ali , Ankit D. Oza","doi":"10.1016/j.jmgm.2025.109203","DOIUrl":"10.1016/j.jmgm.2025.109203","url":null,"abstract":"<div><div>In this research work, the double perovskite Cs2AuXY6 (X = Sb, Bi; Y = Cl, Br) is explored as an absorber material in perovskite solar cells (PSCs). Computational simulations were performed by using Generalised Gradient Approximation along with Perdew–Burke–Ernzerhof (GGA-PBE) and modified Becke–Johnson (mBJ) exchange-correlation potential within the WIEN2K software to study the physical properties of Cs<sub>2</sub>AuXY<sub>6</sub>. Studied compounds have a cubic crystal structure with space group Fm3m (No 225). Electronic bandgap values for Cs2AuBiCl6, Cs2AuSbCl6 are 0.61, 0.24. Cs2AuBiBr6 is a semimetal (considering GGA-PBE) and has band gaps of 1.62, 1.12, and 0.59 eV (with mBJ), which are very close to the required band gap for solar cell applications according to the Shockley–Queisser limit. In addition to the above, the Optical result shows higher absorption and optical conductivity with minimal reflection in the visible and infrared regions, making them good absorbent materials for PSC. Moreover, the temperature-dependent thermoelectric nature of these compounds was explored by the BoltzTraP code, and the mechanical elastic constants were investigated by the charpin method, which follows the Born stability condition. Therefore, Cs<sub>2</sub>AuXY<sub>6</sub>-based PSCs are considered potential materials for charge transport layers, perovskite absorber layers, and conventional halide perovskite compounds.</div></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"142 ","pages":"Article 109203"},"PeriodicalIF":3.0,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145459033","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}
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