Electronic Theses and Dissertation

Pendahuluan: Kanker merupakan salah satu penyebab utama kematian di dunia, dengan hampir 10 juta kematian pada tahun 2020, menurut WHO. Kanker tiroid adalah jenis kanker endokrin yang insidensinya terus meningkat, dipengaruhi oleh gaya hidup dan lingkungan. Pengobatan kanker tiroid bervariasi tergantung stadium, mulai dari operasi hingga terapi tambahan, seperti thyrotropin suppression dan terapi radioaktif, namun kegagalan terapi sering terjadi akibat mutasi genetik. Polimorfisme dan kompleksitas jalur sinyal, yang mengganggu proses apoptosis, berkontribusi pada resistensi kanker. Protein BCL-2 dan Ki-67, yang terkait dalam proses apoptosis dan proliferasi, telah diteliti sebagai target potensial terapi kanker. Seiring tren back to nature, penelitian menunjukkan potensi bahan alam seperti daun nilam (Pogostemon cablin Benth.) dalam menginduksi apoptosis pada sel kanker. Penelitian ini bertujuan untuk mengidentifikasi interaksi senyawa aktif nilam aceh dengan protein BCL-2 dan Ki-67 pada kanker tiroid menggunakan metode molecular docking dan simulasi dinamika molekular.
Metode: Penelitian ini menggunakan metode in silico yang dilakukan dengan 24 senyawa metabolit sekunder daun nilam yang diperoleh dari hasil GC-MS dengan protein target BCL-2 dan Ki-67 melalui Pyrx 0.9 dan divisualisasikan melalui BIOVIA Discovery Studio 2021. Senyawa paling berpotensi selanjutnya dilakukan simulasi dinamika molekuler dengan menggunakan YASARA.
Hasil: Hasil dari moleculer docking menunjukkan bahwa senyawa yang memiliki afinitas dan stabilitas yag paling baik kemudian diikuti pola interaksi indentik dengan ligan kontrol pada kompleks ligan dan protein BCL-2 adalah Caryophyllene dan Alpha-(delta)-Guaiene. Selanjutnya senyawa yang memiliki afinitas dan stabilitas yag paling baik kemudian diikuti pola interaksi indentik dengan ligan kontrol pada kompleks ligan dan protein Ki-67 adalah Globulol, dan Cedran-diol, 8S,13-. 2. Ligan uji Caryophyllene memiliki potensi sebagai inhibitor protein anti-apoptosis BCL-2 dengan menunjukkan stabilitas paling baik berdasarkan parameter binding free energy, RMSD ligand movement, radius of gyration, dan RMSF melalui simulasi dinamika molekular. Ligan uji Globulol memiliki potensi sebagai inhibitor protein proliferasi Ki-67 dengan menunjukkan stabilitas paling baik berdasarkan parameter binding free energy, RMSD ligand movement, radius of gyration, dan RMSF.
Kesimpulan: Ligan uji Caryophyllene diprediksi paling berpotensi untuk menghambat protein anti-apoptosis BCL-2 dan Ligan uji Globulol diprediksi paling berpotensi untuk menghambat protein Ki-67 berdasarkan hasil docking molekuler dan simulasi dinamika molekuler.
Kata Kunci: BCL-2, Ki-67, Daun Nilam, Kanker Tiroid

Introduction: Cancer is one of the leading causes of death worldwide, with nearly 10 million deaths recorded in 2020, according to WHO. Thyroid cancer, a type of endocrine cancer, has shown an increasing incidence, is influenced by lifestyle and environmental factors. Treatments for thyroid cancer vary depending on the stage, ranging from surgery to additional therapies, such as thyrotropin suppression and radioactive therapy; however, treatment failure often occurs due to genetic mutations. Polymorphisms and the complexity of signaling pathways that disrupt apoptosis contribute to cancer resistance. The BCL-2 and Ki-67 proteins, which are involved in apoptosis and proliferation processes, have been studied as potential therapeutic targets for cancer. In line with the back-to-nature trend, research has shown the potential of natural products, such as Patchouli leaf (Pogostemon cablin Benth.), in inducing apoptosis in cancer cells. This study aims to identify the interaction of active compounds from Aceh Patchouli with the BCL-2 and Ki-67 proteins in thyroid cancer using molecular docking and molecular dynamic simulation methods. Methods: This research utilized in silico methods with 24 secondary metabolite compounds from Patchouli leaf, obtained from GC-MS results, targeted at the BCL-2 and Ki-67 proteins through Pyrx 0.9 and visualized using BIOVIA Discovery Studio 2021. The most promising compounds were further analyzed through molecular dynamic simulations using YASARA. Results: The molecular docking results indicate that two compounds with the best affinity and stability, showing interaction patterns identical to the control ligand in the BCL-2 protein-ligand complex, were Caryophyllene and Alpha-(delta)-Guaiene. As for the Ki-67 protein-ligand complex, the compounds with the best affinity and stability, showing interaction patterns identical to the control ligand, were Globulol and Cedran-diol, 8S,13-. The test ligand, Caryophyllene, has a potential as an inhibitor of the anti-apoptotic protein BCL-2, showing the best stability based on binding free energy parameters, RMSD ligand movement, radius of gyration, and RMSF through molecular dynamic simulation. The test ligand, Globulol, has a potential as an inhibitor of the proliferation protein Ki-67, demonstrating the best stability based on binding free energy parameters, RMSD ligand movement, radius of gyration, and RMSF. Conclusion: The test ligand, Caryophyllene, is predicted to have the highest potential to inhibit the anti-apoptotic protein BCL-2, whilst the test ligand, Globulol, is predicted to have the highest potential to inhibit the Ki-67 protein based on molecular docking and molecular dynamic simulation results. Keywords: BCL-2, Ki-67, Patchouli Leaf, Thyroid Cancer