Bridging Molecular Docking to Molecular Dynamics to Enlighten Recognition Processes of Tailored D-A/D-A-D Types' AIEgens with HSA/BSA

Abstract

Fluorescence imaging-assisted photodynamic therapy (PDT) allows accurate tumor visualization and potentially prevents long-term side effects of cancer. Therefore, the development of photosensitizers emitting light, particularly in the near-infrared region (NIR), is essential for enhancing the efficacy of cancer therapy. On this premise, the formation of a stabilized complex between an organic dye and a target macromolecule improves fluorescence efficiency. In this scope, we performed a detailed molecular dock-ing study of Donor (D)-Acceptor (A) or D-A-D type luminogens with two blood proteins; namely bovine serum albumin (BSA) and human serum albumin (HSA), which appeared as robust carriers of several pharmaceuticals against preliminary cancer diseases. Our results revealed that the binding scores of the Dn-An or Dn-An-Dn:BSA complexes ranged from -8.5 to -11.7 kcal/mol while Dn-An or Dn-An-Dn:HSA complexes showed scores varying from -8.4 to -10.5 kcal/mol. Subsequently, molecular dynamics simu-lations were also performed for the best-docked ligands: macromolecule complexes; namely D1A1D1:BSA and D1A1:HSA, to enlighten various structural parameters. Based on the predicted root-mean-square deviation (RMSD) values (on average), the D1A1D1:BSA complex was found to be 0.319 nm, while the D1A1:HSA complex was determined as 0.284 nm. In addition, the root-mean-square fluctuations (RMSF) analyses (on average) revealed that D1A1D1:BSA (0.152 nm) was slightly more flexible than D1A1:HSA (0.160 nm).

Keywords

• BSA
• HSA
• luminogens
• molecular docking
• molecular dynamics

References

1. Ajloo, D., Fazeli, S. M., & Amirani, F. J. (2013). Interaction of Cationic and Anionic Phthalocyanines with Adenosine Deaminase, Molecular Dynamics Simulation and Docking Studies. Computational Molecular Bioscience, 03(04), 81–93. https://doi.org/10.4236/cmb.2013.34010
2. Akdogan, Y., Reichenwallner, J., & Hinderberger, D. (2012). Evidence for Water-Tuned Structural Differences in Proteins: An Approach Emphasizing Variations in Local Hydrophilicity. PLoS ONE, 7(9), e45681. https://doi.org/10.1371/journal.pone.0045681
3. Avti, P., Chauhan, A., Shekhar, N., Prajapat, M., Sarma, P., Kaur, H., Bhattacharyya, A., Kumar, S., Prakash, A., Sharma, S., & Medhi, B. (2021). Computational basis of SARS-CoV 2 main protease inhibition: an insight from molecular dynamics simulation based findings. Journal of Biomolecular Structure and Dynamics, 1–11. https://doi.org/10.1080/07391102.2021.1922310
4. Benet, L. Z., Hosey, C. M., Ursu, O., & Oprea, T. I. (2016). BDDCS, the Rule of 5 and drugability. Advanced Drug Delivery Reviews, 101, 89–98. https://doi.org/10.1016/j.addr.2016.05.007
5. Chakraborty, D., Musib, D., Saha, R., Das, A., Raza, M. K., Ramu, V., Chongdar, S., Sarkar, K., & Bhaumik, A. (2022). Highly stable tetradentate phosphonate-based green fluorescent Cu-MOF for anticancer therapy and antibacterial activity. Materials Today Chemistry, 24, 100882. https://doi.org/10.1016/j.mtchem.2022.100882
6. Chandra, S., Qureshi, S., Chopra, D., Dwivedi, A., & Ray, R. S. (2022). Involvement of Type‐I and Type‐II Photodynamic Reactions in Photosensitization of Fragrance Ingredient 2‐acetonaphthone. Photochemistry and Photobiology, 98(5), 1050–1058. https://doi.org/10.1111/php.13593
7. Cox, T. R. (2021). The matrix in cancer. Nature Reviews Cancer, 21(4), 217–238. https://doi.org/10.1038/s41568-020-00329-7
8. 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(1), 42717. https://doi.org/10.1038/srep42717

9. Daneman, R., & Prat, A. (2015). The Blood–Brain Barrier. Cold Spring Harbor Perspectives in Biology, 7(1), a020412. https://doi.org/10.1101/cshperspect.a020412
10. Debela, D. T., Muzazu, S. G., Heraro, K. D., Ndalama, M. T., Mesele, B. W., Haile, D. C., Kitui, S. K., & Manyazewal, T. (2021). New approaches and procedures for cancer treatment: Current perspectives. SAGE Open Medicine, 9, 205031212110343. https://doi.org/10.1177/20503121211034366
11. Deng, K., Li, C., Huang, S., Xing, B., Jin, D., Zeng, Q., Hou, Z., & Lin, J. (2017). Recent Progress in Near Infrared Light Triggered Photodynamic Therapy. Small, 13(44), 1702299. https://doi.org/10.1002/smll.201702299
12. Dennington, R., Keith, T., & Millam, J. (2009). GaussView, Version 5.0.8. GaussView, Version 5.0.8.
13. Dewaele, M., Maes, H., & Agostinis, P. (2010). ROS-mediated mechanisms of autophagy stimulation and their relevance in cancer therapy. Autophagy, 6(7), 838–854. https://doi.org/10.4161/auto.6.7.12113
14. Ertl, P., Rohde, B., & Selzer, P. (2000). Fast Calculation of Molecular Polar Surface Area as a Sum of Fragment-Based Contributions and Its Application to the Prediction of Drug Transport Properties. Journal of Medicinal Chemistry, 43(20), 3714–3717. https://doi.org/10.1021/jm000942e
15. Escudero, A., Carrillo-Carrión, C., Castillejos, M. C., Romero-Ben, E., Rosales-Barrios, C., & Khiar, N. (2021). Photodynamic therapy: photosensitizers and nanostructures. Materials Chemistry Frontiers, 5(10), 3788–3812. https://doi.org/10.1039/D0QM00922A
16. Fan, M., Xu, Z., Liu, M., Jiang, Y., Zheng, X., Yang, C., Law, W.-C., Ying, M., Wang, X., Shao, Y., Swihart, M. T., Xu, G., Yong, K.-T., & Tang, B. Z. (2021). Recent advances of luminogens with aggregation-induced emission in multi-photon theranostics. Applied Physics Reviews, 8(4), 041328. https://doi.org/10.1063/5.0071142
17. Frisch, M. J., Trucks, G. W., Schlegel, H. B., Scuseria, G. E., Robb, M. A., Cheeseman, J. R., Scalmani, G., Barone, V., Mennucci, B., Petersson, G. A., Nakatsuji, H., Caricato, M., Li, X., Hratchian, H. P., Izmaylov, A. F., Bloino, J., Zheng, G., Sonnenberg, J. L., Hada, M., … Fox, D. J. (2010). Gaussian09 Revision D.01, Gaussian Inc. Wallingford CT. In Gaussian 09 Revision C.01.
18. He, S., Song, J., Qu, J., & Cheng, Z. (2018). Crucial breakthrough of second near-infrared biological window fluorophores: design and synthesis toward multimodal imaging and theranostics. Chemical Society Reviews, 47(12), 4258–4278. https://doi.org/10.1039/C8CS00234G
19. Hishikawa, H., Kaibori, M., Tsuda, T., Matsui, K., Okumura, T., Ozeki, E., & Yoshii, K. (2019). Near-infrared fluorescence imaging and photodynamic therapy with indocyanine green lactosomes has antineoplastic effects for gallbladder cancer. Oncotarget, 10(54), 5622–5631. https://doi.org/10.18632/oncotarget.27193
20. Hong, G., Antaris, A. L., & Dai, H. (2017). Near-infrared fluorophores for biomedical imaging. Nature Biomedical Engineering, 1(1), 0010. https://doi.org/10.1038/s41551-016-0010
21. Islam, R., Parves, M. R., Paul, A. S., Uddin, N., Rahman, M. S., Mamun, A. Al, Hossain, M. N., Ali, M. A., & Halim, M. A. (2020). A molecular modeling approach to identify effective antiviral phytochemicals against the main protease of SARS-CoV-2. Journal of Biomolecular Structure and Dynamics, 1–12. https://doi.org/10.1080/07391102.2020.1761883
22. Li, Y., Liu, S., Ni, H., Zhang, H., Zhang, H., Chuah, C., Ma, C., Wong, K. S., Lam, J. W. Y., Kwok, R. T. K., Qian, J., Lu, X., & Tang, B. Z. (2020). ACQ‐to‐AIE Transformation: Tuning Molecular Packing by Regioisomerization for Two‐Photon NIR Bioimaging. Angewandte Chemie International Edition, 59(31), 12822–12826. https://doi.org/10.1002/anie.202005785
23. Lin, H., Lin, Z., Zheng, K., Wang, C., Lin, L., Chen, J., & Song, J. (2021). Near‐Infrared‐II Nanomaterials for Fluorescence Imaging and Photodynamic Therapy. Advanced Optical Materials, 9(9), 2002177. https://doi.org/10.1002/adom.202002177
24. Lokhande, K. B., Ballav, S., Yadav, R. S., Swamy, K. V., & Basu, S. (2022). Probing intermolecular interactions and binding stability of kaempferol, quercetin and resveratrol derivatives with PPAR-γ: docking, molecular dynamics and MM/GBSA approach to reveal potent PPAR- γ agonist against cancer. Journal of Biomolecular Structure and Dynamics, 40(3), 971–981. https://doi.org/10.1080/07391102.2020.1820380
25. Mfouo-Tynga, I., & Abrahamse, H. (2015). Cell Death Pathways and Phthalocyanine as an Efficient Agent for Photodynamic Cancer Therapy. International Journal of Molecular Sciences, 16(12), 10228–10241. https://doi.org/10.3390/ijms160510228
26. Miller, K. D., Nogueira, L., Mariotto, A. B., Rowland, J. H., Yabroff, K. R., Alfano, C. M., Jemal, A., Kramer, J. L., & Siegel, R. L. (2019). Cancer treatment and survivorship statistics, 2019. CA: A Cancer Journal for Clinicians, 69(5), 363–385. https://doi.org/10.3322/caac.21565
27. Mishra, D., Maurya, R. R., Kumar, K., Munjal, N. S., Bahadur, V., Sharma, S., Singh, P., & Bahadur, I. (2021). Structurally modified compounds of hydroxychloroquine, remdesivir and tetrahydrocannabinol against main protease of SARS-CoV-2, a possible hope for COVID-19: Docking and molecular dynamics simulation studies. Journal of Molecular Liquids, 335, 116185. https://doi.org/10.1016/j.molliq.2021.116185
28. Moriguchi, I., Hirono, S., Nakagome, I., & Hirano, H. (1994). Comparison of Reliability of log P Values for Drugs Calculated by Several Methods. Chemical and Pharmaceutical Bulletin, 42(4), 976–978. https://doi.org/10.1248/cpb.42.976
29. Rubtsova, N. I., Hart, M. C., Arroyo, A. D., Osharovich, S. A., Liebov, B. K., Miller, J., Yuan, M., Cochran, J. M., Chong, S., Yodh, A. G., Busch, T. M., Delikatny, E. J., Anikeeva, N., & Popov, A. V. (2021). NIR Fluorescent Imaging and Photodynamic Therapy with a Novel Theranostic Phospholipid Probe for Triple-Negative Breast Cancer Cells. Bioconjugate Chemistry, 32(8), 1852–1863. https://doi.org/10.1021/acs.bioconjchem.1c00295
30. Sun, Y., Lei, Z., & Ma, H. (2022). Twisted aggregation-induced emission luminogens (AIEgens) contribute to mechanochromism materials: a review. Journal of Materials Chemistry C. https://doi.org/10.1039/D2TC02512D
31. Surti, M., Patel, M., Adnan, M., Moin, A., Ashraf, S. A., Siddiqui, A. J., Snoussi, M., Deshpande, S., & Reddy, M. N. (2020). Ilimaquinone (marine sponge metabolite) as a novel inhibitor of SARS-CoV-2 key target proteins in comparison with suggested COVID-19 drugs: designing, docking and molecular dynamics simulation study. RSC Advances, 10(62), 37707–37720. https://doi.org/10.1039/D0RA06379G
32. Trott, O., & Olson, A. J. (2009). AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. Journal of Computational Chemistry, NA-NA. https://doi.org/10.1002/jcc.21334
33. Wang, D., Lee, M. M. S., Xu, W., Shan, G., Zheng, X., Kwok, R. T. K., Lam, J. W. Y., Hu, X., & Tang, B. Z. (2019). Boosting Non‐Radiative Decay to Do Useful Work: Development of a Multi‐Modality Theranostic System from an AIEgen. Angewandte Chemie International Edition, 58(17), 5628–5632. https://doi.org/10.1002/anie.201900366
34. Wang, J., Zhang, L., & Li, Z. (2021). Aggregation‐Induced Emission Luminogens with Photoresponsive Behaviors for Biomedical Applications. Advanced Healthcare Materials, 10(24), 2101169. https://doi.org/10.1002/adhm.202101169
35. Xu, P., Kang, F., Yang, W., Zhang, M., Dang, R., Jiang, P., & Wang, J. (2020). Molecular engineering of a high quantum yield NIR-II molecular fluorophore with aggregation-induced emission (AIE) characteristics for in vivo imaging. Nanoscale, 12(8), 5084–5090. https://doi.org/10.1039/C9NR09999A
36. Xu, S., Duan, Y., & Liu, B. (2020). Precise Molecular Design for High‐Performance Luminogens with Aggregation‐Induced Emission. Advanced Materials, 32(1), 1903530. https://doi.org/10.1002/adma.201903530
37. Xu, W., Wang, D., & Tang, B. Z. (2021). NIR‐II AIEgens: A Win–Win Integration towards Bioapplications. Angewandte Chemie, 133(14), 7552–7563. https://doi.org/10.1002/ange.202005899