Journal of Biomolecular Structure & Dynamics最新文献

{"title":"Computational insights into overcoming resistance mechanisms in targeted therapies for advanced breast cancer: focus on EGFR and HER2 co-inhibition.","authors":"Osama Abdulaziz, Farhan R Khan, Nahed S Alharthi, Hayaa M Alhuthali, Ali Hazazi, Hind A Alzahrani, Amal F Gharib, Ohud A Alsalmi, Nahed M Hawsawi, Abdulfattah Y Alhazmi","doi":"10.1080/07391102.2024.2301766","DOIUrl":"10.1080/07391102.2024.2301766","url":null,"abstract":"<p><p>In the present study, the formation of a heterodimer involving both epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) has been explored as a potential therapeutic mechanism to inhibit the progression of breast cancer. Virtual screening using molecular docking resulted in the three hit compounds (<b>ZINC08382411</b>, <b>ZINC08382438</b>, and <b>ZINC08382292</b>) with minimum binding scores and commonly binding to both receptors. Further, MD simulation analysis of these complexes illustrated the high stability of these compounds with EGFR and HER2. RMSD showed that <b>ZINC08382411</b> displayed the most stable RMSD of 2 - 3 Å when bound to both receptors, suggesting to have strong compatibility with the active site of the receptor. Hydrogen bond analysis showed that <b>ZINC08382411</b> forms the maximum number of H-bonds (2 to 3) in both EGFR and HER2 bound complexes, with the highest occupancy of 62% and 79%, respectively. Binding free energy calculation showed that <b>ZINC08382411</b> possesses maximum affinity towards both the receptors with ΔG_bind = -129.628 and -164.063 kJ/mol, respectively. This approach recognizes the significance of EGFR and HER2 in breast cancer development and aims to disrupt their collaborative signaling, which is known to promote the antagonistic behavior of cancer cells. By focusing on this EGFR/HER2 heterodimer, the study offers a promising avenue for identifying a potential candidate (<b>ZINC08382411)</b> that may inhibit breast cancer cell growth and potentially improve patient outcomes. The study's findings may contribute to the ongoing efforts to advance breast cancer treatment strategies.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"4215-4226"},"PeriodicalIF":2.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139485601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Screening and unveiling antibacterial mechanism of dandelion phenolic extracts against <i>Staphylococcus aureus</i> by inhibiting intracellular Na⁺-K⁺ ATPase based on molecular docking and molecular dynamics simulation.","authors":"Xuefeng Xu, Xiang Wang, Pujun Xie","doi":"10.1080/07391102.2023.2300123","DOIUrl":"10.1080/07391102.2023.2300123","url":null,"abstract":"<p><p><i>Staphylococcus aureus</i> is one of the most frequently food-contaminated incidence of healthcare-associated Gram-positive bacteria. The antibacterial function and mechanism of phenolic compounds from dandelion are still unclear. Herein, this work aims to screen one of dandelion phenolic extracts with the strongest antibacterial function from its organ such as flower, stem, leaf and root, and to reveal its antibacterial mechanism. The results indicated dandelion flower phenolic extract (DFPE) containing the highest content of caffeic acid, followed by luteolin and luteolin-7-O-glucoside. They, especially caffeic acid and luteolin-7-O-glucoside, played a key role in making the bacterial cellular-membrane ruptured against the bacteria. The leakage of the intracellular substances (adenosine triphosphate and Na⁺-K⁺ ATPase) was further confirmed. Conventional hydrogen bond, pi-anion, pi-alkyl were involved in the interaction between caffeic acid or luteolin-7-O-glucoside and Na⁺-K⁺ ATPase. Additionally, the dynamic equilibrium of the liganded ATPase complex were achieved after 105 ns, and the lower values from the radius of gyration and solvent accessible surface area in the complex demonstrated the highly tight and compact structure of the liganded protein. The highest free binding energy (ΔG_bind = -47.80 kJ/mol) between Na⁺-K⁺ ATPase and luteolin-7-O-glycloside was observed. Overall, DFPE can be used as an effective anti-bacterial agent due to the contribution of its bioactive ingredients such as caffeic acid and luteolin-7-O-glucoside for membrane-breaking.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"3802-3813"},"PeriodicalIF":2.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139087023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 approved drugs with ALDH1A1 inhibitory potential aimed at enhancing chemotherapy sensitivity in cancer cells: an in-silico drug repurposing approach.","authors":"Sanjay Kumar Paul, Abdelmadjid Guendouzi, Agniswar Banerjee, Abdelkrim Guendouzi, Rajen Haldar","doi":"10.1080/07391102.2023.2300127","DOIUrl":"10.1080/07391102.2023.2300127","url":null,"abstract":"<p><p>The aldehyde dehydrogenase 1A1 (ALDH1A1) also known as retinal dehydrogenase, is an enzyme normally involved in the cellular metabolism, development and detoxification processes in healthy cells. However, it's also considered a cancer stem cell marker and its high levels of expression in several cancers, including breast, lung, ovarian, and colon cancer have been associated with poor prognosis and resistance to chemotherapy. Given its crucial role in chemotherapy resistance by detoxification of chemotherapeutic drugs, ALDH1A1 has attracted significant research interest as a potential therapeutic target for cancer. Though a few synthetic inhibitors of ALDH1A1 have been synthesized and their efficacy has been proved in-vitro and in-vivo studies, none of them have passed clinical trials so far. In this scenario, we have performed an in-silico study to verify whether any of the already approved drugs used for various purposes has the ability to inhibit catalytic activity of ALDH1A1, so that they can be repurposed for cancer therapy. Keeping in mind the feasibility of repurposing in a larger population we have selected the approved drugs from five widely used drug categories such as antibiotic, antiviral, antifungal, anti diabetic and antihypertensive for screening. Computational techniques like molecular docking, molecular dynamics simulations and MM-PBSA binding energy calculation have been used in this study to screen the approved drugs. Based on the logical analysis of results, we propose that three drugs - telmisartan, irbesartan and maraviroc can inhibit the catalytic activity of ALDH1A1 and thus can be repurposed to increase chemotherapy sensitivity in cancer cells.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"3830-3844"},"PeriodicalIF":2.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139377686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An <i>in silico</i> analysis of the interaction of marine sponge-derived bioactive compounds with type 2 diabetes mellitus targets DPP-4 and PTP1B.","authors":"Jillian Dominique P Roxas, Maria Angela D San Juan, Al Rey C Villagracia, Rafael A Espiritu","doi":"10.1080/07391102.2024.2301751","DOIUrl":"10.1080/07391102.2024.2301751","url":null,"abstract":"<p><p>Type 2 diabetes is a medical condition involving elevated blood glucose levels resulting from impaired or improper insulin utilization. As the number of type 2 diabetes cases increases each year, there is an urgent need to develop novel drugs having new targets and/or complementing existing therapeutic protocols. In this regard, marine sponge-derived compounds hold great potential due to their potent biological activity and structural diversity. In this study, a small library of 50 marine sponge-derived compounds were examined for their activity towards type 2 diabetes targets, namely dipeptidyl peptidase-4 (DPP-4) and protein tyrosine phosphatase 1B (PTP1B). The compounds were first subjected to molecular docking on protein models based on their respective co-crystal structures to assess binding free energies (BFE) and conformations. Clustering analysis yielded BFE that ranged from 24.54 kcal/mol to -9.97 kcal/mol for DPP-4, and from -4.98 kcal/mol to -8.67 kcal/mol for PTP1B. Interaction analysis on the top ten compounds with the most negative BFE towards each protein target showed similar intermolecular interactions and key interacting residues as in the previously solved co-crystal structure. These compounds were subjected to absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiling to characterize drug-likeness and combining the results from these analyses, (<i>S</i>)-6'-debromohamacanthin B was identified as a potential multi-target inhibitor of DPP-4 and PTP1B, having favorable protein interaction, no Lipinski violations, good gastrointestinal (GI) tract absorption, blood-brain barrier (BBB) penetration, and no predicted toxicity. Finally, the interaction of (<i>S</i>)-6'-debromohamacanthin B with the two proteins was validated using molecular dynamics simulations over 100 ns through RMSD, radius of gyration, PCA, and molecular mechanics Poisson-Boltzmann surface area (MMPBSA) confirming favorable interactions with the respective proteins.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"4138-4151"},"PeriodicalIF":2.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139377682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>In silico</i> approaches for predicting natural compounds with therapeutic potential and vaccine candidates against <i>Streptococcus equi</i>.","authors":"Bernardo Mirabal, Bruno Silva Andrade, Sarah Pereira Andrade Souza, Igor Batista Dos Santos Oliveira, Tarcisio Silva Melo, Fabrício Santos Barbosa, Arun Kumar Jaiswal, Nubia Seyffert, Ricardo Wagner Portela, Siomar de Castro Soares, Vasco Azevedo, Roberto Meyer, Sandeep Tiwari, Thiago Luiz de Paula Castro","doi":"10.1080/07391102.2023.2301056","DOIUrl":"10.1080/07391102.2023.2301056","url":null,"abstract":"<p><p>Equine strangles is a prevalent disease that affects the upper respiratory in horses and is caused by the Gram-positive bacterium <i>Streptococcus equi</i>. In addition to strangles, other clinical conditions are caused by the two <i>S. equi</i> subspecies, <i>equi</i> and <i>zooepidemicus</i>, which present relevant zoonotic potential. Treatment of infections caused by <i>S. equi</i> has become challenging due to the worldwide spreading of infected horses and the unavailability of effective therapeutics and vaccines. Penicillin treatment is often recommended, but multidrug resistance issues arised. We explored the whole genome sequence of 18 <i>S. equi</i> isolates to identify candidate proteins to be targeted by natural drug-like compounds or explored as immunogens. We considered only proteins shared among the sequenced strains of subspecies <i>equi</i> and <i>zooepidemicus</i>, absent in the equine host and predicted to be essential and involved in virulence. Of these, 4 proteins with cytoplasmic subcellular location were selected for molecular docking with a library of 5008 compounds, while 6 proteins were proposed as prominent immunogens against <i>S. equi</i> due to their probabilities of behaving as adhesins. The molecular docking analyses revealed the best ten ligands for each of the 4 drug target candidates, and they were ranked according to their binding affinities and the number of hydrogen bonds for complex stability. Finally, the natural 5-ring compound C₂₅H₂₀F₃N₅O₃ excelled in molecular dynamics simulations for the increased stability in the interaction with UDP-N-acetylenolpyruvoylglucosamine reductase (MurB). This research paves the way to developing new therapeutics to minimize the impacts caused by <i>S. equi</i> infections.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"4013-4027"},"PeriodicalIF":2.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139491480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of mutations on O⁶-methylguanine methyl transferase structure and its interactions: molecular dynamics simulation study.","authors":"Marzieh Gharouni, Hamid Mosaddeghi","doi":"10.1080/07391102.2023.2300133","DOIUrl":"10.1080/07391102.2023.2300133","url":null,"abstract":"<p><p>O⁶-methylguanine DNA methyl transferase (MGMT) is a significant vehicle for the cellular clearance of alkyl lesions, particularly the methyl group of the O-6 and O-4 positions of guanine and thymine, respectively. Many publications have studied the correlation between polymorphisms in MGMT and susceptibility to various cancers. In the present study, we investigated the consequence of L84F, common single-nucleotide polymorphism, K125E, site-specific mutagenesis, and L84F/K125E on conformation, stability, and behavior of MGMT in the free form and interaction with proliferating cell nuclear antigen (PCNA) and DNA as partners in the biochemical network by using molecular dynamics simulation method. Our results showed that all free variants of MGMT differed from the native form. However, among all free variants of MGMT, the L84F/K125E variant exhibited similar properties compared with the wild-type. In contrast, in complex modes, only amino acid residues of the L84F variant are involved in the interactions with PCNA and DNA somewhat differently relative to the wild-type. Furthermore, L84F SNP showed the highest binding free energy compared to other variants and native forms. These alterations in the amino acids and binding free energy of L84F relative to the native are the reasons for changing its region connection compared to the native form. Therefore, we propose conducting further investigations into the impact of inhibitors or chemotherapeutic agents to assess their effectiveness on MGMT variants compared to the wild-type, aiming to reduce the cost of cancer treatment that will depend on inhibiting native MGMT protein.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"3929-3941"},"PeriodicalIF":2.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139087031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repurposing FDA-approved drugs as NLRP3 inhibitors against inflammatory diseases: machine learning and molecular simulation approaches.","authors":"Vipul Agarwal, Rajesh Haldhar, Abdurahman Hajinur Hirad, Bilal Ahmed, Sang Beom Han, Anugya Gupta, Vinit Raj, Sangkil Lee","doi":"10.1080/07391102.2024.2308072","DOIUrl":"10.1080/07391102.2024.2308072","url":null,"abstract":"<p><p>Activation of NLRP3 (NOD-like receptor family, pyrin domain-containing protein 3) has been associated with multiple chronic pathologies, including diabetes, atherosclerosis, and rheumatoid arthritis. Moreover, histone deacetylases (HDACs), specifically HDAC6 is required for the NLRP3 inflammasome to assemble and activate. Thus, NLRP3 serves as an attractive target for the development of novel therapeutic approaches. Several companies are now attempting to develop specific modulators of the NLRP3 inflammasome, but only a handful of small molecules of NLRP3 inflammasome inhibitors, such as MCC950 and Tranilast, are currently available for clinical use. However, their use is limited due to severe side effects and short half-lives. Thus, the repurposing of FDA-approved drugs with NLRP3 inhibitory activity is needed. The present study was aimed at repurposing preexisting drugs that might act as safe and effective NLRP3 inhibitors. A library of 2,697 FDA-approved drugs was screened for binding with NLRP3 (PDB: 7ALV) using Glide (Schrödinger). The top seven FDA-approved drugs with potential binding affinities were selected based on docking scores and subjected to ADMET profiling using pkCSM and SwissADME. The binding of the ADMET-favorable FDA-approved drugs to NLRP3 was validated using MMGBSA (Prime) and Molecular Dynamics (Desmond) in the Schrödinger suite. ADMET profiling revealed that of the seven best docking drugs, empagliflozin and citicoline had good drug-likeness properties. Moreover, MMGBSA analysis and molecular dynamics demonstrated that empagliflozin and citicoline exhibited stable ligand-NLRP3 interactions in the presence of solvents. This study sheds light on the ability of various FDA-approved drugs to act as NLRP3 inhibitors.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"4327-4339"},"PeriodicalIF":2.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139944159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 against VP40 protein of Marburg virus by integrating molecular modeling and dynamics approaches.","authors":"Muhammad Saeed, Mubarak A Alamri, Muhammad Abdul Rehman Rashid, Muhammad Rizwan Javed, Farrukh Azeem, Zarmina Bashir, Abdullah R Alanzi, Ziyad Tariq Muhseen, Shahad Youseff Almusallam, Khadim Hussain","doi":"10.1080/07391102.2023.2300134","DOIUrl":"10.1080/07391102.2023.2300134","url":null,"abstract":"<p><p>Marburg virus (MV) is a highly etiological agent of haemorrhagic fever in humans and has spread across the world. Its outbreaks caused a 23-90% human death rate. However, there are currently no authorized preventive or curative measures yet. VP40 is the MV matrix protein, which builds protein shell underneath the viral envelope and confers hallmark filamentous. VP40 alone is able to induce assembly and budding of filamentous virus-like particles (VLPs), which resemble authentic virions. As a result, this research is credited with clarifying the function of VP40 and leading to the discovery of new therapeutic targets effective in combating MV disease (MVD). Virtual screening, molecular docking and molecular dynamics (MD) simulation were used to find the putative active chemicals based on a 3D pharmacophore model of the protein's active site cavity. Initially, andrographidine-C, a potent inhibitor was selected for the development of the pharmacophore model. Later, a library of 30,000 compounds along with the andrographidine-C was docked against VP40 protein. Three best hits including avanafil, diuvaretin and macrourone were subjected to further MD simulation analysis, as these compounds had better binding affinities as compared to andrographidine-C. Furthermore, throughout the 100 ns simulations, the back bone of VP40 protein in presence of avanafil, diuvaretin and macrourone remained stable which was further validated by MM-PBSA analysis. Additionally, all of these compounds depict maximum drug-like properties. The predicted drugs based on the ligand, avanafil, diuvaretin and macrourone could be exploited and developed as an alternative or complementary therapy for the treatment of MVD.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"3942-3955"},"PeriodicalIF":2.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139097854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibitory potential of furanocoumarins against cyclin dependent kinase 4 using integrated docking, molecular dynamics and ONIOM methods.","authors":"Srutishree Sarma, Dikshita Dowerah, Moumita Basumatary, Ambalika Phonglo, Ramesh Ch Deka","doi":"10.1080/07391102.2023.2300755","DOIUrl":"10.1080/07391102.2023.2300755","url":null,"abstract":"<p><p>Cyclin Dependent Kinase 4 (CDK4) is vital in the process of cell-cycle and serves as a G1 phase checkpoint in cell division. Selective antagonists of CDK4 which are in use as clinical chemotherapeutics cause various side-effects in patients. Furanocoumarins induce anti-cancerous effects in a range of human tumours. Therefore, targeting these compounds against CDK4 is anticipated to enhance therapeutic effectiveness. This work intended to explore the CDK4 inhibitory potential of 50 furanocoumarin molecules, using a comprehensive approach that integrates the processes of docking, drug-likeness, pharmacokinetic analysis, molecular dynamics simulations and ONIOM (Our own N-layered Integrated molecular Orbital and Molecular mechanics) methods. The top five best docked compounds obtained from docking studies were screened for subsequent analysis. The molecules displayed good pharmacokinetic properties and no toxicity. Epoxybergamottin, dihydroxybergamottin and notopterol were found to inhabit the ATP-binding zone of CDK4 with substantial stability and negative binding free energy forming hydrogen bonds with key catalytic residues of the protein. Notopterol exhibiting the highest binding energy was subjected to ONIOM calculations wherein the hydrogen bonding interactions were retained with significant negative interaction energy. Hence, through these series of computerised methods, notopterol was screened as a potent CDK4 inhibitor and can act as a starting point in successive processes of drug design.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"3974-4003"},"PeriodicalIF":2.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139377687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 inhibitor phytoconstituents for Influenza A H3N2: an <i>in silico</i> approach.","authors":"Rajan Rolta, Deeksha Salaria, Olatomide A Fadare, Racheal Y Fadare, Gladson David Masih, Ajay Prakash, Bikash Medhi","doi":"10.1080/07391102.2024.2305313","DOIUrl":"10.1080/07391102.2024.2305313","url":null,"abstract":"<p><p>Influenza A virus subtype H3N2 is a highly infectious respiratory virus that is responsible for global seasonal flu epidemics. The current study was designed to investigate the antiviral activity of 150 phytocompounds of North Western Himalayas medicinal plants by molecular docking. Two target proteins of hemagglutinin of influenza virus A (PDB ID 4WE8) and Influenza virus H3N2 nucleoprotein - R416A mutant (PDB ID 7NT8) are selected for this study. Molecular docking was done by AutoDock vina tool, toxicity and drug-likeness prediction was done by protox II and Moleinspiration. MD simulation of best protein-ligand complexes was done by using Gromacs, version 2021.5. Molecular docking and toxicity data revealed that clicoemodin and rumexocide showed the best binding with both target proteins 4WEB & 7NT8. Clicoemodin showed the -7.5 KJ/mol binding energy with 4WE8 and 7NT8. Similarly, rumexoside showed the -7.6 KJ/mol binding energy with 4WE8 and -7.6 KJ/mol with 7NT8. Furthermore, Molecular dynamic simulation and MMPBSA binding free energy validated the stability of protein-ligand complexes. The current study suggested that clicoemodin and rumexocide are the promising inhibitors of H3N2 proteins hemagglutinin of influenza virus A and Influenza virus H3N2 nucleoprotein - R416A mutant, though there is further <i>in vitro</i> and <i>in vivo</i> validation is required.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"4287-4296"},"PeriodicalIF":2.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139511925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}