Simulasi Dinamika Molekuler Kompleks Protein Nukleokapsid Mutan SARS-CoV-2 Dengan Antibodi Imunoglobulin G (IgG)

Tjahyani, Wenny Maylina Mulyo (2026) Simulasi Dinamika Molekuler Kompleks Protein Nukleokapsid Mutan SARS-CoV-2 Dengan Antibodi Imunoglobulin G (IgG). Other thesis, Institut Teknologi Sepuluh Nopember.

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Abstract

Coronavirus Disease 2019 (COVID-19) merupakan penyakit yang disebabkan oleh Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Munculnya berbagai mutasi pada virus ini berpotensi menyebabkan perubahan struktur protein yang dapat memengaruhi pengenalan oleh sistem imun maupun efektivitas vaksin yang sebagian besar menargetkan protein Spike (S). Oleh karena itu, protein nukleokapsid (N) mulai dikembangkan sebagai kandidat antigen alternatif karena memiliki tingkat konservasi dan imunogenisitas yang tinggi. Pada penelitian ini, dilakukan analisis interaksi serta kestabilan kompleks antara protein nukleokapsid SARS-CoV-2 mutan dari Jawa Timur, Jawa Tengah, dan Jawa Barat dengan antibodi imunoglobulin G (IgG) menggunakan pendekatan molecular docking dan molecular dynamics secara in silico. Penelitian diawali dengan pemodelan struktur tiga dimensi protein nukleokapsid menggunakan I-TASSER. Struktur antibodi IgG diperoleh dari Protein Data Bank (PDB ID: 7CM4), kemudian dilakukan identifikasi daerah Complementarity Determining Region (CDR) menggunakan NovoPro. Proses molecular docking dilakukan menggunakan server ClusPro 2.0, sedangkan evaluasi afinitas ikatan dilakukan menggunakan PRODIGY. Kompleks hasil docking selanjutnya disimulasikan menggunakan perangkat lunak GROMACS 2024.4 dengan force field AMBER99SB-ILDN selama 10 ns. Analisis kestabilan kompleks dilakukan berdasarkan parameter Root Mean Square Deviation (RMSD), Root Mean Square Fluctuation (RMSF), Radius of Gyration (Rg), Solvent Accessible Surface Area (SASA), dan jumlah ikatan hidrogen (hydrogen bond). Hasil molecular docking menunjukkan bahwa seluruh protein nukleokapsid mampu berinteraksi dengan antibodi IgG melalui ikatan hidrogen dan interaksi hidrofobik pada daerah Complementarity Determining Region (CDR). Kompleks wild type memiliki afinitas pengikatan tertinggi dengan nilai energi bebas ikatan (ΔG) sebesar −12,5 kcal/mol, diikuti oleh Jawa Tengah (−12,4 kcal/mol), Jawa Timur (−11,8 kcal/mol), dan Jawa Barat (−11,5 kcal/mol). Analisis molecular dynamics berdasarkan parameter Root Mean Square Deviation (RMSD), Root Mean Square Fluctuation (RMSF), Radius of Gyration (Rg), Solvent Accessible Surface Area (SASA), dan jumlah ikatan hidrogen menunjukkan bahwa seluruh variasi mutan kompleks antigen–antibodi mampu mempertahankan kestabilan strukturnya selama simulasi 10 ns. Hasil penelitian juga menunjukkan bahwa seluruh varian mutan pada protein nukleokapsid SARS-CoV-2 tidak mengganggu interaksi dengan antibodi IgG, sehingga protein nukleokapsid mutan dari Jawa Timur, Jawa Tengah, dan Jawa Barat tetap berpotensi untuk dikembangkan lebih lanjut sebagai kandidat antigen alternatif dalam pengembangan vaksin.
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Coronavirus Disease 2019 (COVID-19) is an infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The emergence of various mutations in this virus may induce structural changes in viral proteins, potentially affecting immune recognition as well as the efficacy of vaccines that primarily target the spike (S) protein. Therefore, the nucleocapsid (N) protein has emerged as a promising alternative antigen candidate due to its high sequence conservation and immunogenicity. This study analyzed the interaction and stability of complexes formed between mutant SARS-CoV-2 nucleocapsid proteins from East Java, Central Java, and West Java and immunoglobulin G (IgG) antibodies using in silico molecular docking and molecular dynamics approaches. Three-dimensional structures of the nucleocapsid proteins were generated using I-TASSER. The IgG antibody structure was obtained from the Protein Data Bank (PDB ID: 7CM4), and the Complementarity-Determining Regions (CDRs) were identified using NovoPro. Molecular docking was performed using the ClusPro 2.0 server, and binding affinity was evaluated with PRODIGY. The docked complexes were subsequently subjected to a 10 ns molecular dynamics simulation using GROMACS 2024.4 with the AMBER99SB-ILDN force field. Complex stability was assessed based on the Root Mean Square Deviation (RMSD), Root Mean Square Fluctuation (RMSF), Radius of Gyration (Rg), Solvent Accessible Surface Area (SASA), and the number of hydrogen bonds. The molecular docking results demonstrated that all nucleocapsid proteins interacted with the IgG antibody through hydrogen bonds and hydrophobic interactions within the Complementarity-Determining Regions (CDRs). The wild-type complex exhibited the highest binding affinity, with a binding free energy (ΔG) of −12.5 kcal/mol, followed by the Central Java (−12.4 kcal/mol), East Java (−11.8 kcal/mol), and West Java (−11.5 kcal/mol) mutant complexes. Molecular dynamics analysis indicated that all mutant antigen–antibody complexes maintained structural stability throughout the 10 ns simulation. Furthermore, the results suggest that mutations in the SARS-CoV-2 nucleocapsid protein did not disrupt its interaction with the IgG antibody, indicating that the nucleocapsid proteins from East Java, Central Java, and West Java remain promising alternative antigen candidates for vaccine development.

Item Type:	Thesis (Other)
Uncontrolled Keywords:	Imunoglobulin G (IgG), Molecular docking, Molecular dynamics, Protein nukleokapsid, SARS-CoV-2, Immunoglobulin G (IgG), Molecular docking, Molecular dynamics, Nucleocapsid protein, SARS-CoV-2
Subjects:	Q Science Q Science > QR Microbiology Q Science > QR Microbiology > QR180 Immunology
Divisions:	Faculty of Science and Data Analytics (SCIENTICS) > Chemistry > 47201-(S1) Undergraduate Thesis
Depositing User:	Wenny Maylina Mulyo Tjahyani
Date Deposited:	04 Aug 2026 07:18
Last Modified:	04 Aug 2026 07:18
URI:	http://repository.its.ac.id/id/eprint/143392

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