Penambatan Molekuler Senyawa Aktif Temu Kunci (Boesenbergia pandurata) Sebagai Inhibitor Matrix Metalloproteinase-1

Abstract

Matrix metalloproteinase-1 (MMP-1) merupakan enzim pendegradasi kolagen yang aktivitasnya dipicu oleh sinar ultraviolet (UV). MMP-1 memiliki pengaruh langsung dalam photoaging, sehingga diperlukan inhibitor untuk menghambat aktivitas MMP-1 untuk mencegah penuaan kulit. Temu kunci (Boesenbergia pandurata) diketahui memiliki senyawa aktif yang potensial dalam menghambat penuaan kulit, namun potensi dari masing-masing senyawa bioaktif temu kunci sebagai inhibitor MMP-1 secara in silico belum diketahui. Penelitian ini bertujuan menguji potensi tanaman temu kunci sebagai inhibitor MMP-1 melalui penambatan molekuler dan analisis jenis interaksi yang terbentuk. Pada tahap awal, senyawa aktif temu kunci diseleksi melalui penapisan virtual menggunakan YASARA Structure serta prediksi bioavailabilitas dan toksisitas melalui pkCSM dan Protox online tool. Selanjutnya, dilakukan penambatan molekuler menggunakan YASARA Structure serta visualisasi 2D dan 3D menggunakan Discovery Studio Visualizer. Sebanyak enam ligan terbaik dipilih sebagai kandidat terbaik berdasarkan hasil penapisan virtual, prediksi bioavailabilitas, serta prediksi toksisitas. Ligan-ligan uji tersebut meliputi helichrysetin, panduratin D, pinocembrin chalcone, cardamonin, 5,7-dimethoxyflavone, dan tectochrysin. Hasil terbaik penambatan molekuler ditunjukkan oleh tectochrysetin dengan nilai ΔGbind sebesar -9,59 kkal/mol dan Kd sebesar 0,094 μM.

Matrix metalloproteinase-1 (MMP-1) is a collagen-degrading enzyme whose activity is triggered by ultraviolet (UV) light. MMP-1 has a direct effect on photoaging, so an inhibitor is needed to inhibit MMP-1 activity to prevent skin aging. Fingerroot (Boesenbergia pandurata) are known to have active compounds that have the potential to inhibit skin aging. However, there is no study regarding the potency of each fingerroot bioactive compound as MMP-1 inhibitor through in silico research yet. This study aims to test the potential of fingerroot as an MMP-1 inhibitor through molecular docking and analysis of the types of interactions formed. In the early stages, the active compounds of fingerroot were selected through virtual screening using the YASARA Structure and checked for bioavailability and toxicity prediction through pkCSM and Protox online tools. The ligand selected were subjected to molecular docking using YASARA Structure and 2D and 3D visualization using Discovery Studio Visualizer. Six ligands were selected as best candidate based on virtual screening, bioavailability, and toxicity result. Those ligands are helichrysetin, panduratin D, pinocembrin chalcone, cardamonin, 5,7-dimethoxyflavone, dan tectochrysin. The best results are shown by tectochrysetin with -9,59 kcal/mol ΔGbind score dan Kd 0,094 μM.