Yunita, Khadijah Cahya (2018) Interaksi Obat dengan HLA-B Pasien Stevens-Johnson Syndrome dan Toxic Epidermal Necrolysis di RSUD Dr. Saiful Anwar Malang (Studi Molecular Docking). Sarjana thesis, Universitas Brawijaya.
Abstract
Pendahuluan: Stevens-Johnson Syndrome dan Toxic Epidermal Necrolysis merupakan reaksi simpang obat yang tidak terkait dosis terapi namun akibat dari respon imun yang tidak dapat diprediksi. Reaksi hipersensitivitas tipe IVc berperan dalam apoptosis keratinosit diawali dengan aktivasi sel T CD8+/CTL melalui konsep p-i, yakni obat berikatan dengan MHC dari APC atau TCR. Metode: Data primer berasal dari identifikasi HLA-B pasien yang pernah atau sedang mengalami SJS-TEN akibat terpicu oleh obat yang dikonsumsinya dan dirawat di RSUD Dr. Saiful Anwar Malang. Pertama, membuat model 3D HLA-B yang dimiliki pasien dari protein sequence-nya, yakni HLA-B*13:01:01:01, B*15:02:01, B*15:21:01:01, B*18:01:01:01, B*18:02, B*35:01:01:01, B*35:03:01:01, B*37:01:01:01, B*38:02:01, B*40:01:02:01, B*51:02:02, B*58:01:01:01, dan B*51:01:02, kualitas dan validitas model tersebut dianalisis. Kemudian mengunduh molekul 3D Acetaminophen, Allopurinol, Amoxicillin, Ibuprofen, Carbamazepine, Nevirapine, dan Sulfasalazine yang dikonsumsi pasien. Kedua, melakukan molecular docking dan visualisasi interaksi antara HLA-B dengan obat tersebut. Ketiga, menganalisis hasil dengan melihat binding affinity, lokasi ikatan, dan jenis peristiwa fisik yang terjadi. Hasil penelitian: Semua model HLA-B tersebut memiliki sequence identity >90%, GMQE >0.7, dan persentase plot Ramachandran >98%. Semua obat tersebut memiliki berat molekul rendah. Semua kompleks ikatan antara obat dan HLA-B tersebut terjadi dalam peptide-binding cleft, yakni pada rantai α1, α2 α- helix, serta dasar β-sheet dengan membentuk ikatan non-kovalen bersama residu asam amino HLA-B untuk membentuk ikatan stabil dan menghasilkan binding affinity terkuat. Kesimpulan: Terdapat interaksi antara obat yang dikonsumsi dengan HLA-B yang dimiliki pasien SJS-TEN di RSUD Dr. Saiful Anwar Malang yang dianalisis menggunakan molecular docking
English Abstract
Background: Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis is an adverse drug reaction of a non-dose related type due to an unpredictable immune response. Type IVc hypersensitivity reaction plays a role in keratinocyte apoptosis due to the CD8+/CTL activation through the p-i concept when the drug bind to MHC or TCR molecule. Methods: The primary data comes from the identification of HLA-B patients who have or are experiencing SJS-TEN triggered by drugs they consumed and treated at RSUD Dr. Saiful Anwar Malang. First, build a 3D model of patient’s HLA-B from its protein sequence, HLA-B*13:01:01:01, B*15:02:01, B*15:21:01:01, B*18:01:01:01, B*18:02, B*35:01:01:01, B*35:03:01:01, B*37:01:01:01, B*02:38:01, B*40:01:02:01, B*51:02:02, B*58:01:01:01, and B*51:01:02, analyze the quality and validation of the models. Then download the 3D molecule of Acetaminophen, Allopurinol, Amoxicillin, Ibuprofen, Carbamazepine, Nevirapine, and Sulfasalazine that is consumed by the patients. Second, do the molecular docking procedure and visualize the interaction between the drug and the HLA-B. Third, analyze the results according to the knowledge based, the empirical-based, and the force field based scoring function by looking at the binding affinity, location, and type of the physical event. Results: All of the mentioned HLA-B models have sequence identity >90%, GMQE >0.7, and the percentage of the Ramachandran plot >98%. All of the mentioned drugs have low molecular weight. All of the interaction complex between the drug and the HLA-B occurs in peptide-binding cleft on α1, α2 helix, and the basis of β-sheets by forming non-covalent bond with the amino acid residue to form stable bonds and generate the highest binding affinity. Conclusion: There is interaction between prescribed drugs and patient’s HLABs in RSUD Dr. Saiful Anwar Malang analyzed by molecular docking method.
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| Item Type: | Thesis (Sarjana) |
|---|---|
| Identification Number: | SKR/FK/2018/429/051900008 |
| Uncontrolled Keywords: | SJS-TEN, ADR, HLA-B, molecular docking, SJS-TEN, ADR, locus B HLA, molecular docking |
| Subjects: | 600 Technology (Applied sciences) > 616 Diseases > 616.5 Diseases of integument / Skin--Diseases > 615.506 Skin--Diseases--Treatment > 615.506 1 Skin--Diseases--Chemotherapy |
| Divisions: | Fakultas Kedokteran > Pendidikan Dokter |
| Depositing User: | Nur Cholis |
| Date Deposited: | 21 May 2020 03:25 |
| Last Modified: | 21 Oct 2021 07:08 |
| URI: | http://repository.ub.ac.id/id/eprint/167732 |
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