Studi Dinamika Molekuler Pada Kompleks Antibodi IgM Dengan Antigen Protein Nukleokapsid SARS-CoV-2 Termutasi

Nugraha, Subhan (2026) Studi Dinamika Molekuler Pada Kompleks Antibodi IgM Dengan Antigen Protein Nukleokapsid SARS-CoV-2 Termutasi. Other thesis, Institut Teknologi Sepuluh Nopember.

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Abstract

Pengembangan vaksin Coronavirus 2019 (COVID-19) masih menjadi topik menarik untuk dipelajari karena tingkat mutasi virus SARS-CoV-2 yang tinggi. Penelitian ini berfokus pada pengembangan antigen alternatif SARS-CoV-2 di mana protein nukleokapsid (N) SARS-CoV-2 mewakili sebagai kandidat potensial. Di sini, kami melaporkan studi in silico tentang kompleks antigen-antibodi IgM, meliputi stabilitas, kekuatan, dan perilakunya dalam larutan air. Sampel protein N merupakan strain SARS-CoV-2 yang paling banyak ditemukan di Pulau Jawa. Data urutan antigen diperoleh dari GISAID dan NCBI, sedangkan struktur antibodi diambil dari RCSB PDB. Molecular docking dilakukan menggunakan ClusPro 2.0 dan dianalisis menggunakan PRODIGY untuk memperoleh data energi bebas ikatan (ΔG), konstanta disosiasi (Kd), dan kontak antar residu. Molecular dynamics dilakukan menggunakan perangkat lunak GROMACS 2026.1 melalui serangkaian tahapan, meliputi persiapan struktur, pembuatan topologi, solvasi, penambahan ion, minimisasi energi, serta ekuilibrasi NVT dan NPT. Analisis trajektori dilakukan dengan menghitung Root Mean Square Deviation (RMSD), Root Mean Square Fluctuation (RMSF), ikatan hidrogen, Radius of Gyration (Rg), dan Solvent Accessible Surface Area (SASA). Dari simulasi molecular dynamics selama 10 ns, keempat varian menunjukkan karakteristik stabilitas interaksi yang berbeda. Varian Wuhan sebagai wild type menampilkan kestabilan struktural tertinggi dengan fluktuasi RMSD dan RMSF paling rendah, profil Rg yang stabil, serta ikatan hidrogen yang terjaga setelah fase ekuilibrium awal, didukung nilai binding affinity sebesar -12,8 kkal/mol, sehingga menjadi referensi pembanding yang kuat. Di antara ketiga varian lokal, varian Jawa Timur menunjukkan profil kestabilan paling meyakinkan, ditandai dengan RMSD yang mencapai ekuilibrium, ikatan hidrogen yang konsisten di rentang 390–450 ikatan, pemampatan antarmuka yang terkontrol, dan nilai binding affinity tertinggi sebesar -11,5 kkal/mol. Varian Jawa Barat memiliki nilai binding affinity yang hampir setara yakni -11,3 kkal/mol, namun dinamika strukturalnya lebih fluktuatif dengan penurunan Rg dan SASA paling drastis, mengindikasikan reorganisasi konformasi yang kemungkinan belum mencapai ekuilibrium penuh pada akhir simulasi. Varian Jawa Tengah menunjukkan konformasi yang cukup teratur dengan reorganisasi ikatan hidrogen yang menguntungkan di akhir simulasi, namun memperoleh nilai binding affinity terendah sebesar -7,6 kkal/mol yang mencerminkan afinitas pengikatan paling lemah di antara varian lainnya.
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The development of a 2019 Coronavirus (COVID-19) vaccine are still interesting topic to be studied due to the high mutation rate of the SARS-CoV-2 virus. This study focuses on the development of alternative SARS-CoV-2 antigens, in which the SARS-CoV-2 nucleocapsid (N) protein represents a potential candidate. Here, we report an in silico study of the IgM antibody-antigen complex, including its stability, strength, and behavior in water solution. The N protein sample represents the most common SARS-CoV-2 strain found in Java. Antigen sequence data were obtained from GISAID and NCBI, while antibody structures were taken from RCSB PDB. Molecular docking was performed by using ClusPro 2.0 and analyzed by using PRODIGY to obtain data on binding free energy (ΔG), dissociation constant (Kd), and inter-residue contacts. Molecular dynamics were performed by using GROMACS 2026.1 software through stages including structure preparation, topology creation, solvation, ion addition, energy minimization, and NVT & NPT equilibration. Trajectory analysis was performed by calculating Root Mean Square Deviation (RMSD), Root Mean Square Fluctuation (RMSF), hydrogen bonds, Radius of Gyration (Rg), and Solvent Accessible Surface Area (SASA). From the 10 ns molecular dynamics simulation, the four variants showed different interaction stability characteristics. The Wuhan variant as the wild type showed the highest structural stability with the lowest RMSD and RMSF fluctuations, a stable Rg profile, and maintained hydrogen bonds after the initial equilibrium phase, supported by a binding affinity value of -12.8 kcal/mol, making it a strong comparative reference. Among the three local variants, the East Java variant showed the most convincing stability profile, characterized by RMSD reaching equilibrium, consistent hydrogen bonds in the range of 390–450 bonds, controlled interface compression, and the highest binding affinity value of -11.5 kcal/mol. The West Java variant has a nearly equivalent binding affinity value of -11.3 kcal/mol, but its structural dynamics are more fluctuating with the most drastic decrease in Rg and SASA, indicating a conformational reorganization that may not have reached full equilibrium at the end of the simulation. The Central Java variant shows a fairly regular conformation with favorable hydrogen bond reorganization at the end of the simulation, but obtains the lowest binding affinity value of -7.6 kcal/mol, reflecting the weakest binding affinity among the others.

Item Type:	Thesis (Other)
Uncontrolled Keywords:	Antibodi IgM, Molecular Docking, Molecular Dynamics, Protein Nukleokapsid, SARS-CoV-2, IgM Antibody, Molecular Docking, Molecular Dynamics, Nucleocapsid Protein, SARS-CoV-2
Subjects:	Q Science > QR Microbiology > QR180 Immunology
Divisions:	Faculty of Science and Data Analytics (SCIENTICS) > Chemistry > 47201-(S1) Undergraduate Thesis
Depositing User:	Subhan Nugraha
Date Deposited:	04 Aug 2026 05:37
Last Modified:	04 Aug 2026 05:37
URI:	http://repository.its.ac.id/id/eprint/143067

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