MENORAH ABISAG INDRAWATI WIJAYA, - (2022) SIMULASI DINAMIKA MOLEKUL PADA NANOBODIKORTISOL DENGAN PENAMBAHAN PENANDA HISTIDIN DAN SISTEIN SEBAGAI RANCANGAN PEMBUATAN KIT DETEKSI. Skripsi thesis, Sekolah Tinggi Farmasi Indonesia.
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Abstract
Simulasi dinamika molekul adalah teknik komputasi yang dapat mensimulasikan interaksi protein dan ligan dalam pelarut dengan proses pemanasan sebagai satu kesatuan sistem untuk mengamati interaksi kimia yang terjadi selama waktu yang ditentukan. Nanobodi VHH adalah antibodi kelas baru yang memiliki spesifisitas, afinitas, dan kemudahan produksi. Penelitian ini melanjutkan modifikasi struktur natif nanobodi VHH-kortisol (Nb-Cor) dan mutan T53I dengan penambahan histidin untuk pemurnian nanobodi dan sistein untuk deteksi kortisol pada alat deteksi. Penelitian ini bertujuan untuk memodelkan kompleks Nb-Cor dan memperoleh informasi afinitas Nb-Cor terhadap penambahan histidin dan sistein. Preparasi Nb-Cor natif dan mutan dilakukan dengan program MODELLER. Evaluasi hasil model dilakukan dengan metode skor DOPE, plot Ramachandran, dan Z-score. Simulasi dinamika molekul dilakukan dengan program pmemd pada Amber20 dengan suhu pemanasan maksimal 299 K selama 120 ns untuk menghasilkan trajektori simulasi RMSD dan RMSF serta analisis pengikatan energi bebas MMPBSA dan ikatan hidrogen. Hasilnya RMSD kedua sistem stabil dan nilainya berada di bawah rentang 2,5 Å. Fluktuasi RMSF Nb-Cor natif mempengaruhi pengikatan ligan pada CDR1 dan CDR2. Pengikatan energi bebas natif -36,89 kkal/mol dan mutan -38,47 kkal/mol. Durasi ikatan hidrogen mutan lebih lama daripada natif. Kesimpulannya Nb-Cor-Cys-His mutan lebih baik daripada Nb-Cor-Cys-His natif karena tidak terpengaruhnya CDR1 dan CDR2. --- Molecular dynamics simulation is a computational technique that can simulate the interaction of proteins and ligands in dissolution by heating process as a unit system for chemical interactions that occur over a specified time. VHH nanobody is a new class of antibodies that has specificity, affinity, and ease of production. This study continued modifying the native structure of the VHH nanobody-cortisol (Nb-Cor) and the T53I mutant with the addition of histidine for the purification of nanobodies and cysteine to detect cortisol in the detection device. This study aims to model the Nb-Cor complex and obtain information on the affinity of Nb-Cor to the addition of histidine and cysteine. The native and mutant Nb-Cor preparations were carried out with the MODELLER program. The model evaluations were carried out using the DOPE score method, the Ramachandran plot, and the Zscore. Molecular dynamics simulations were carried out using the pmemd program on Amber20 with a maximum heating temperature of 299 K for 120 ns to produce RMSD and RMSF trajectory simulations along with analysis of binding energy of MMPBSA and hydrogen bond. As a result, RMSD of both systems was stable and their range value was below 2,5 Å. Fluctuations of Nb-Cor native RMSF affected ligand binding to CDR1 and CDR2. Native binding free energy was -36,89 kcal/mol and the mutant -38,47 kcal/mol. Hydrogen bond duration on mutant was longer than native. In conclusion, the Nb-Cor-Cys-His mutant structure was better than the Nb-Cor-Cys-His native structure because it didn’t affect CDR1 and CDR2.
| Item Type: | Thesis (Skripsi) |
|---|---|
| Uncontrolled Keywords: | Nanobodi, Kortisol, Histidin, Sistein, Simulasi Dinamika Molekul --- Nb-Cor, Histidine, Cysteine , Protein Folding, Energy Binding |
| Subjects: | Q Science > Q Science (General) |
| Divisions: | Program Studi S1 Farmasi |
| Depositing User: | pustakawan - - |
| Date Deposited: | 14 Sep 2024 04:56 |
| Last Modified: | 14 Sep 2024 04:57 |
| URI: | http://repository.stfi.ac.id/id/eprint/1193 |
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