In Silico Screening of SARS-CoV-2 RBD-Targeting Antibodies Using HDOCK and PRODIGY
Main Article Content
Abstract
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.
Keywords
HDOCK, monoclonal antibody, PRODIGY, protein-protein docking, RBD, SARS-CoV-2.
Article Details
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
References
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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