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Journals / Black Sea Journal of Engineering and Science / 2026 / Cilt: 9 Sayı: 2

In Silico Investigation of the Molecular-Level Interactions of Phenolic Compounds in Propolis with the Mechanosensitive Piezo1 Channel

Bişar Amaç(HARRAN UNIVERSITY, FACULTY OF HEALTH SCIENCES, DEPARTMENT OF PERFUSION)0000-0003-0320-4239
Ömer Göç(HARRAN UNIVERSITY, FACULTY OF HEALTH SCIENCES, DEPARTMENT OF PERFUSION)0000-0002-3047-6232
Pages
633–645
Publication Date
2026-03-15
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AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

The findings contribute to understanding the molecular basis of Piezo1-mediated mechanotransduction and provide a structural reference for future experimental studies, particularly in the context of cardiovascular mechanotransduction.

📌 3 Key Takeaways

🎯
Objective & Hypothesis:The aim of this study is to evaluate the interactions between the A, B and C chains of the Piezo1 (6B3R) protein and selected natural phenolic and flavonoid compounds using molecular docking methods, and to comparatively examine chain-specific binding profiles.
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Key Findings & Data:The Piezo1 structure was obtained from the Protein Data Bank (PDB ID: 6B3R), and protein and ligand preparations were carried out under physiological pH conditions.
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Conclusion & Impact:The findings contribute to understanding the molecular basis of Piezo1-mediated mechanotransduction and provide a structural reference for future experimental studies, particularly in the context of cardiovascular mechanotransduction.
🔬Design:Modeling & Simulation
📍Scope:Comprehensive Sample
⚙️Variables:Piezo1 · 6B3R · Molecular docking

Abstract

The aim of this study is to evaluate the interactions between the A, B and C chains of the Piezo1 (6B3R) protein and selected natural phenolic and flavonoid compounds using molecular docking methods, and to comparatively examine chain-specific binding profiles. Molecular docking analyses were performed using Schrödinger Maestro software. The Piezo1 structure was obtained from the Protein Data Bank (PDB ID: 6B3R), and protein and ligand preparations were carried out under physiological pH conditions. Separate Glide grids were defined for chains A, B, and C; docking operations were performed in Glide SP and XP modes. Binding affinities were evaluated based on docking scores and Glide emodel values, and 2D and 3D interaction analyses were performed for the best poses. Additionally, the physicochemical and ADME properties of the selected ligands were calculated. Docking analyses revealed that ligand binding behaviour differed significantly between Piezo1 chains. In particular, epigallocatechin gallate (EGCG) and epicatechin gallate exhibited strong and stable binding profiles across all chains, with the highest binding affinity observed in the C chain. It was determined that the strong interactions were supported by multiple hydrogen bonds and aromatic interactions. This study reveals the chain-specific ligand binding properties of Piezo1 and demonstrates that natural polyphenolic compounds can form strong interactions with this mechanosensitive ion channel. The findings contribute to understanding the molecular basis of Piezo1-mediated mechanotransduction and provide a structural reference for future experimental studies, particularly in the context of cardiovascular mechanotransduction.

Özet

The aim of this study is to evaluate the interactions between the A, B and C chains of the Piezo1 (6B3R) protein and selected natural phenolic and flavonoid compounds using molecular docking methods, and to comparatively examine chain-specific binding profiles. Molecular docking analyses were performed using Schrödinger Maestro software. The Piezo1 structure was obtained from the Protein Data Bank (PDB ID: 6B3R), and protein and ligand preparations were carried out under physiological pH conditions. Separate Glide grids were defined for chains A, B, and C; docking operations were performed in Glide SP and XP modes. Binding affinities were evaluated based on docking scores and Glide emodel values, and 2D and 3D interaction analyses were performed for the best poses. Additionally, the physicochemical and ADME properties of the selected ligands were calculated. Docking analyses revealed that ligand binding behaviour differed significantly between Piezo1 chains. In particular, epigallocatechin gallate (EGCG) and epicatechin gallate exhibited strong and stable binding profiles across all chains, with the highest binding affinity observed in the C chain. It was determined that the strong interactions were supported by multiple hydrogen bonds and aromatic interactions. This study reveals the chain-specific ligand binding properties of Piezo1 and demonstrates that natural polyphenolic compounds can form strong interactions with this mechanosensitive ion channel. The findings contribute to understanding the molecular basis of Piezo1-mediated mechanotransduction and provide a structural reference for future experimental studies, particularly in the context of cardiovascular mechanotransduction.

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Cite This Article

Amaç, B., Göç, Ö. (2026). In Silico Investigation of the Molecular-Level Interactions of Phenolic Compounds in Propolis with the Mechanosensitive Piezo1 Channel. Black Sea Journal of Engineering and Science, Cilt: 9 Sayı: 2, 633–645. https://doi.org/10.34248/bsengineering.1859600

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References (33)

  1. Alam, M., Gulzar, M., Akhtar, M. S., Rashid, S., Zulfareen, Tanuja, Shamsi, A., & Hassan, M. I. (2024). Epigallocatechin-3-gallate therapeutic potential in human diseases: Molecular mechanisms and clinical studies. Molecular Biomedicine, 5(1), 73. https://doi.org/10.1186/s43556-024-00240-9
  2. Amangeldinova, M., Ersatır, M., Necip, A., Cimentepe, M., Kudrina, N., Terletskaya, N., Cimentepe, Ö. Ö., Cakır, O., Yilmaz, M. A., & Yıldırım, M. (2025). Green extraction strategies and bioactivity of Rheum cordatum Losinsk: Antioxidant, antimicrobial, and molecular docking insights. Plants, 14(7), 1071. https://doi.org/10.3390/plants14071071
  3. Boulechfar, S., Zellagui, A., Asan-Ozusaglam, M., Bensouici, C., Erenler, R., Yildiz, İ., Tacer, S., Boural, H., & Demirtas, I. (2021). Chemical composition, antioxidant, and antimicrobial activities of two essential oils from Algerian propolis. Zeitschrift für Naturforschung C, 77(3–4), 105–112. https://doi.org/10.1515/znc-2021-0028
  4. Canales Coutiño, B., & Mayor, R. (2021). Mechanosensitive ion channels in cell migration. Cells & Development, 166, 203683. https://doi.org/10.1016/j.cdev.2021.203683
  5. Çimentepe, M., Ünver, H., Necip, A., & Yıldırım, M. (2025). Novel benzimidazole-based cobalt complex: Synthesis, AChE enzyme inhibition, antibacterial and antibiofilm activity against multidrug-resistant bacteria, and computational analysis. Polyhedron, 283, 117861. https://doi.org/10.1016/j.poly.2025.117861
  6. Daina, A., Michielin, O., & Zoete, V. (2017). SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Scientific Reports, 7, 42717. https://doi.org/10.1038/srep42717
  7. Demirbağ, B., Yıldırım, M., Cimentepe, M., Necip, A., Unver, H., & Tiftik, E. N. (2025). Novel vanillin-derived Schiff bases: Synthesis, characterization, antibacterial, enzyme inhibition, antioxidant, and anti-inflammatory activities, and in silico studies. Journal of Molecular Structure, 1338(1), 142320. https://doi.org/10.1016/j.molstruc.2025.142320
  8. Douguet, D., Patel, A., Xu, A., Vanhoutte, P. M., & Honoré, E. (2019). Piezo ion channels in cardiovascular mechanobiology. Trends in Pharmacological Sciences, 40(12), 956–970. https://doi.org/10.1016/j.tips.2019.10.002
  9. Guo, Y. R., & MacKinnon, R. (2017). Structure-based membrane dome mechanism for Piezo mechanosensitivity. eLife, 6, e33660. https://doi.org/10.7554/eLife.33660
  10. Hadidi, M., Liñán-Atero, R., Tarahi, M., Christodoulou, M. C., & Aghababaei, F. (2024). The potential health benefits of gallic acid: Therapeutic and food applications. Antioxidants, 13(8), 1001. https://doi.org/10.3390/antiox13081001
  11. Harwansh, R. K., Deshmukh, R., Shukla, V. P., Khunt, D., Prajapati, B. G., Rashid, S., Ali, N., Elossaily, G. M., Suryawanshi, V. K., & Kumar, A. (2024). Recent advancements in gallic acid-based drug delivery: Applications, clinical trials, and future directions. Pharmaceutics, 16(9), 1202. https://doi.org/10.3390/pharmaceutics16091202
  12. Hyman, A. J., Tumova, S., & Beech, D. J. (2017). Piezo1 channels in vascular development and the sensing of shear stress. Current Topics in Membranes, 79, 37–57. https://doi.org/10.1016/bs.ctm.2016.11.001
  13. Jiang, W., Wijerathne, T. D., Zhang, H., Lin, Y. C., Jo, S., Im, W., Lacroix, J. J., & Luo, Y. L. (2023). Structural and thermodynamic framework for PIEZO1 modulation by small molecules. Proceedings of the National Academy of Sciences of the United States of America, 120(50), e2310933120. https://doi.org/10.1073/pnas.2310933120
  14. Kaya, B., Çevik, U. A., Çiftçi, B., Necip, A., Işik, M., Ay, E. N., Yur, S., Özkay, Y., Beydemir, Ş., & Kaplancıklı, Z. A. (2025b). Design, synthesis, and molecular docking studies of novel pyrazoline-thiazoles as cholinesterase dual-target inhibitors for the treatment of Alzheimer’s disease. ACS Omega, 10(34), 38427–38439. https://doi.org/10.1021/acsomega.5c01055
  15. Kaya, B., Tahtacı, H., Çiftçi, B., Duran, H. E., Necip, A., Işık, M., & Beydemir, Ş. (2025a). Discovery of hydrazine-clubbed thiazoles as potential antidiabetic agents: Synthesis, biological evaluation, and molecular docking studies. Drug Development Research, 86(1), e70060. https://doi.org/10.1002/ddr.70060
  16. Liu, Y., Xu, Y. Q., Long, Y. Y., Xiao, H., Ma, Y. Y., & Li, Y. W. (2025). Mechanosensitive channel Piezo1 in calcium dynamics: Structure, function, and emerging therapeutic strategies. Frontiers in Molecular Biosciences, 12, 1693456. https://doi.org/10.3389/fmolb.2025.1693456
  17. Lu, M., Guo, Y., Ji, L., Xue, H., Li, X., & Tan, J. (2025). Insights into interactions between polyphenols and proteins and their applications: An updated overview. Journal of Agriculture and Food Research, 23, 102269. https://doi.org/10.1016/j.jafr.2025.102269
  18. Necip, A. (2025). Natural remedies for type 2 diabetes: Evaluation of phytochemicals with bioinformatics and molecular approaches/ADME/T analysis. Cumhuriyet Science Journal, 46(2), 329–337.
  19. Necip, A., Demirtas, I., Tayhan, S. E., Işık, M., Bilgin, S., Turan, İ. F., İpek, Y., & Beydemir, Ş. (2023). Isolation of phenolic compounds from eco-friendly white bee propolis: Antioxidant, wound-healing, and anti-Alzheimer effects. Food Science & Nutrition, 12(3), 1928–1939. https://doi.org/10.1002/fsn3.3888
  20. Omer, H. H. S., Demirtas, I., Karaca, E., Yarım, M., & Ozen, T. (2024). Investigating the hepatoprotective and antidiabetic properties of cryogenically pulverized Turkish propolis water extracts in streptozotocin-induced diabetic rats. South African Journal of Botany, 174, 927–936.
  21. Otero-Sobrino, Á., Blanco-Carlón, P., Navarro-Aguadero, M. Á., Gallardo, M., Martínez-López, J., & Velasco-Estévez, M. (2023). Mechanosensitive ion channels: Their physiological importance and potential key role in cancer. International Journal of Molecular Sciences, 24(18), 13710. https://doi.org/10.3390/ijms241813710
  22. Pan, X., Wan, R., Wang, Y., Liu, S., He, Y., Deng, B., Luo, S., Chen, Y., Wen, L., Hong, T., Xu, H., Bian, Y., Xia, M., & Li, J. (2022). Inhibition of chemically and mechanically activated Piezo1 channels as a mechanism for ameliorating atherosclerosis with salvianolic acid B. British Journal of Pharmacology, 179(14), 3778–3814. https://doi.org/10.1111/bph.15826
  23. RCSB Protein Data Bank. (2025). Piezo1 structure (PDB ID: 6B3R). Retrieved November 1, 2025, from https://www.rcsb.org/structure/6B3R
  24. Saotome, K., Murthy, S. E., Kefauver, J. M., Whitwam, T., Patapoutian, A., & Ward, A. B. (2018). Structure of the mechanically activated ion channel Piezo1. Nature, 554(7693), 481–486. https://doi.org/10.1038/nature25453
  25. Saritha, K., Alivelu, M., & Mohammad, M. (2024). Drug-likeness analysis, in silico ADMET profiling of compounds in Kedrostis foetidissima (Jacq.) Cogn., and antibacterial activity of the plant extract. In Silico Pharmacology, 12(2), 67. https://doi.org/10.1007/s40203-024-00240-1
  26. Tang, H., Zeng, R., He, E., Zhang, I., Ding, C., & Zhang, A. (2022). Piezo-type mechanosensitive ion channel component 1 (Piezo1): A promising therapeutic target and its modulators. Journal of Medicinal Chemistry, 65(9), 6441–6453. https://doi.org/10.1021/acs.jmedchem.2c00085
  27. Thien, N. D., Hai-Nam, N., Anh, D. T., & Baecker, D. (2024). Piezo1 and its inhibitors: Overview and perspectives. European Journal of Medicinal Chemistry, 273, 116502. https://doi.org/10.1016/j.ejmech.2024.116502
  28. Yıldırım, M., Ünver, H., Necip, A., & Çimentepe, M. (2025c). Design, synthesis, and biological evaluation of novel vanillin-derived hydrazone compounds with antimicrobial, anticancer, and enzyme inhibition activities, along with molecular structure and drug-likeness assessment. Biochemical and Biophysical Research Communications, 775, 152173. https://doi.org/10.1016/j.bbrc.2025.152173
  29. Yıldırım, M., Ünver, H., Necip, A., Çimentepe, M., & Ersatır, M. (2025a). Multifunctional benzimidazolium derivatives as anticancer, antibacterial, and acetylcholinesterase inhibitors: In vitro and molecular docking studies. Archives of Biochemistry and Biophysics, 774, 110630. https://doi.org/10.1016/j.abb.2025.110630
  30. Yıldırım, M., Yasar, E., Necip, A., Cimentepe, M., Öztürk, G., & Kilic, A. (2025b). Boron–ellagic acid hybrids as a molecular arrow: Multi-targeted inhibition of AChE, anticancer activity, and antimicrobial action against MRSA and MDR E. coli, supported by docking analyses. Journal of Molecular Liquids, 440, 128953. https://doi.org/10.1016/j.molliq.2025.128953
  31. Zhang, K., Huang, J., Wang, D., Wan, X., & Wang, Y. (2024). Covalent polyphenols–proteins interactions in food processing: Formation mechanisms, quantification methods, bioactive effects, and applications. Frontiers in Nutrition, 11, 1371401. https://doi.org/10.3389/fnut.2024.1371401
  32. Zhao, M. J., Yin, J. L., Luo, J. H., Ge, Y. S., Huang, C. M., Meng, T. T., Wang, X. Z., Huang, X. H., Chen, L. L., Zhai, Y. Q., Wu, X. B., & Ding, D. F. (2025). Integration of network pharmacology, molecular docking, and experimental validation to identify the effect of EGCG on alleviating chondrocyte inflammatory damage by targeting ER stress–STAT3 crosstalk. Journal of Inflammation Research, 18, 15165–15185. https://doi.org/10.2147/JIR.S564356
  33. Zheng, Q., Zou, Y., Teng, P., Chen, Z., Wu, Y., Dai, X., Li, X., Hu, Z., Wu, S., Xu, Y., Zou, W., Song, H., & Ma, L. (2022). Mechanosensitive channel PIEZO1 senses shear force to induce KLF2/4 expression via CaMKII/MEKK3/ERK5 axis in endothelial cells. Cells, 11(14), 2191. https://doi.org/10.3390/cells11142191