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Pencarian Inhibitor DYRK2 dari Database Bahan Alam Zinc15: Analisis Farmakofor, Simulasi Docking dan Dinamika Molekuler
Abstrak
DYRK2 (Dual-specificity tyrosine phosphorylation-regulated kinase 2) merupakan protein kinase yang memiliki banyak peranan dalam berbagai proses biologis, termasuk pembelahan sel, proliferasi sel, diferensiasi sel, dan apoptosis. DYRK2 diantaranya terlibat dalam regulasi siklus sel dengan cara mengatur aktivitas proteasom 26S sehingga inhibisi aktivitas DYRK2 dapat menghambat fungsi proteasom 26S dan mengurangi proliferasi sel kanker. Secara in vitro, kurkumin menunjukan kemampuan mengurangi proliferasi sel kanker melalui penghambatan enzim DYRK2. Pada penelitian ini, analog kurkumin telah diskrining dari database bahan alam Zinc15 dengan menggunakan model farmakofor yang diperoleg dengan pendekatan berbasis ligan. Hasil skrining kemudian dievaluasi dengan menerapkan teknik docking molekuler dan dinamika molekuler berdasarkan energi interaksi, rata-rata energi pengikatan bebas dan stabilitas interaksi antara ligan dan situs aktif DYRK2. Skrining terhadap 270.547 molekul dari database bahan alam Zinc15 menghasilkan 110 senyawa hit terpilih. Dengan mempertimbangkan hasil simulasi docking dan dinamika molekuler, tiga analog kurkumin prospektif telah dipilih yaitu ZINC000085597244, ZINC000217945958, dan ZINC000217643970. Molekul-molekul ini memiliki kriteria yang lebih baik dibandingkan kurkumin pada beberapa kriteria, seperti energi interaksi, energi pengikatan bebas, dan stabilitas interaksi dengan target. Disimpulkan, senyawa-senyawa ZINC000085597244, ZINC000217945958, dan ZINC000217643970 diprediksi sebagai kandidat potensial untuk obat anti-kanker dengan mekanisme aksi spesifik terhadap DYRK2.
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DOI: https://doi.org/10.25077/jsfk.10.1.100-113.2023
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