Sàng lọc in silico các kháng thể cho thụ thể RBD của SARS-CoV-2 bằng HDOCK và PRODIGY

Tạp chí Khoa học Đại học Đồng Tháp - Tập 14 Số 02S - Trang - 2025
Kieu Nhat Ha1, Kieu Minh Nhan2, Bui Van Thang3, Le Thi Ngoc Tu4, Nguyen Quoc Thai4
1Master's student, Dong Thap University, Vietnam
2Office of Facilities and Project Management, Dong Thap University, Cao Lanh 870000, Vietnam
3Office of Academic Affairs, Dong Thap University, Cao Lanh 870000, Vietnam
4Faculty of Natural Sciences Teacher Education, School of Education, Dong Thap University, Cao Lanh 870000, Vietnam

Tóm tắt

The COVID-19 pandemic and the emergence of SARS-CoV-2 variants underscore the need for potent neutralizing monoclonal antibodies. This study screened 288 antibodies targeting the receptor-binding domain (RBD) of SARS-CoV-2 using the HDOCK platform for protein-protein docking, followed by binding affinity prediction with PRODIGY. Five antibody-RBD complexes (P4A2, C1A-B3, COVOX-150, CC12.1, and 3G10) were identified with high docking scores and binding affinities in the picomolar to nanomolar range (Kd: 8.20 x 10-15 to 1.20 x 10-13 M). Key RBD residues (Tyr473, Leu455, Asn487, Tyr501) were found to drive stable interactions through hydrogen bonds and nonbonded contacts. A strong correlation (R = -0.9, p < 0.001) between HDOCK docking scores, binding free energy (ΔG), and ln(Kd) validates the predictive consistency of this approach. These findings provide a computational framework for prioritizing antibody candidates for further experimental validation, supporting cost-effective antibody development for COVID-19 treatment in Vietnam.

Từ khóa

#HDOCK #monoclonal antibody #PRODIGY #protein-protein docking #RBD #SARS-CoV-2 #SMD

Tài liệu tham khảo

Cowan, J., Amson, A., Christofides, A., & Chagla, Z. (2023). Monoclonal antibodies as COVID-19 prophylaxis therapy in immunocompromised patient populations. Int J Infect Dis, 134, 228-238. https://doi.org/10.1016/j.ijid.2023.06.021

Iyer, A. S., Jones, F. K., Nodoushani, A., Kelly, M., Becker, M., Slater, D., Mills, R., Teng, E., Kamruzzaman, M., Garcia-Beltran, W. F., Astudillo, M., Yang, D., Miller, T. E., Oliver, E., Fischinger, S., Atyeo, C., Iafrate, A. J., Calderwood, S. B., Lauer, S. A., Yu, J., Li, Z., Feldman, J., Hauser, B. M., Caradonna, T. M., Branda, J. A., Turbett, S. E., LaRocque, R. C., Mellon, G., Barouch, D. H., Schmidt, A. G., Azman, A. S., Alter, G., Ryan, E. T., Harris, J. B., & Charles, R. C. (2020). Persistence and decay of human antibody responses to the receptor binding domain of SARS-CoV-2 spike protein in COVID-19 patients. Science Immunology, 5(52), eabe0367. https://doi.org/doi:10.1126/sciimmunol.abe0367

Kaas, Q., Ruiz, M., & Lefranc, M. P. (2004). IMGT/3Dstructure-DB and IMGT/StructuralQuery, a database and a tool for immunoglobulin, T cell receptor and MHC structural data. Nucleic Acids Res, 32(Database issue), D208-210. https://doi.org/10.1093/nar/gkh042

Lai, C. C., Shih, T. P., Ko, W. C., Tang, H. J., & Hsueh, P. R. (2020). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): The epidemic and the challenges. International journal of antimicrobial agents, 55(3), 105924. https://doi.org/10.1016/j.ijantimicag.2020.105924

Li, S. M, Khanh, M. (2012). Steered molecular dynamics-A Promising tool for drug design, Current Bioinformatics, 7(4), 342-351. https://doi.org/10.2174/157489312803901009

Olsen, T. H., Boyles, F., & Deane, C. M. (2022). Observed antibody space: A diverse database of cleaned, annotated, and translated unpaired and paired antibody sequences. Protein Sci, 31(1), 141-146. https://doi.org/10.1002/pro.4205

Premkumar, L., Segovia-Chumbez, B., Jadi, R., Martinez, D. R., Raut, R., Markmann, A., Cornaby, C., Bartelt, L., Weiss, S., Park, Y., Edwards, C. E., Weimer, E., Scherer, E. M., Rouphael, N., Edupuganti, S., Weiskopf, D., Tse, L. V., Hou, Y. J., Margolis, D., Sette, A., Collins, M. H., Schmitz, J., Baric, R. S., & de Silva, A. M. (2020). The receptor binding domain of the viral spike protein is an immunodominant and highly specific target of antibodies in SARS-CoV-2 patients. Sci Immunol, 5(48). https://doi.org/10.1126/sciimmunol.abc8413

Raybould, M. I. J., Kovaltsuk, A., Marks, C., & Deane, C. M. (2021). CoV-AbDab: the coronavirus antibody database. Bioinformatics, 37(5), 734-735. https://doi.org/10.1093/bioinformatics/btaa739

Schrödinger, LLC. (2015). The PyMOL molecular graphics system, Version 1.8. https://pymol.org

Taylor, P. C., Adams, A. C., Hufford, M. M., de la Torre, I., Winthrop, K., & Gottlieb, R. L. (2021). Neutralizing monoclonal antibodies for treatment of COVID-19. Nat Rev Immunol, 21(6), 382-393. https://doi.org/10.1038/s41577-021-00542-x

Wang, C., Li, W., Drabek, D., Okba, N. M. A., van Haperen, R., Osterhaus, A. D. M. E., van Kuppeveld, F. J. M., Haagmans, B. L., Grosveld, F., & Bosch, B.-J. (2020). A human monoclonal antibody blocking SARS-CoV-2 infection. Nature Communications, 11(1), 2251. https://doi.org/10.1038/s41467-020-16256-y

Xue, L. C., Rodrigues, J. P., Kastritis, P. L., Bonvin, A. M., & Vangone, A. (2016). PRODIGY: a web server for predicting the binding affinity of protein–protein complexes. Bioinformatics, 32(23), 3676-3678. https://doi.org/10.1093/bioinformatics/btw514

Yan, Y., Zhang, D., Zhou, P., Li, B., & Huang, S.-Y. (2017). HDOCK: a web server for protein–protein and protein–DNA/RNA docking based on a hybrid strategy. Nucleic Acids Research, 45(W1), W365-W373. https://doi.org/10.1093/nar/gkx407

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Tạp chí Khoa học Đại học Đồng Tháp

Tập 14 Số 02S

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