Indonesian Journal of Medical Chemistry and Bioinformatics


The crystal structure of the human microsomal complex P450 1A2 with alpha-naphthoflavone, a cytochrome P450 (CYP) enzyme is particularly important, as it is abundant in the human liver and alters a more diverse xenobiotic array than any other group of metabolic enzymes. CYP1A2 is abundantly found in the liver and involved in the metabolism of about 10% of clinically used drugs metabolized by CYP enzymes. The current drug discovery and development mostly uses high-throughput screening (HTS). However, this regular method is time-consuming and costly. To address the issue, an advanced drug discovery and development method namely chemical compound database screening through computational methods used in this study as a promising method for chemical compound identification. Molecular docking predicts the conformation and orientation of the ligand in the binding site of the target protein. The results of molecular bonding of 2hi4 protein with 15 chemical compounds showed that three chemical compounds, benzo(a)pyrene, pteryxine, and quinine had satisfactory binding energy levels. A comparison of amino acids seen from 2D visualization shows that there are 7 amino acids in common, namely ALA317, GLY316, ASP313, ASP320, PHE260, PHE226, and THR118.

Bahasa Abstract

Struktur kristal kompleks mikrosomal manusia P450 1A2 dengan alfa-naftatolavon, enzim sitokrom P450 (CYP) sangat penting, karena berlimpah di hati manusia dan mengubah susunan xenobiotik yang lebih beragam daripada kelompok enzim metabolisme lainnya. CYP1A2 banyak ditemukan di hati dan terlibat dalam metabolisme sekitar 10% dari obat yang digunakan secara klinis dimetabolisme oleh enzim CYP. Proses penemuan obat, pengembangan obat baru yang memiliki interaksi potensial dengan target terapeutik adalah konvensional dengan skrining throughput tinggi eksperimental (HTS) tetapi memakan waktu dan mahal. Skrining basis data senyawa kimia melalui metode komputasi telah menjadi metode penting untuk mengidentifikasi senyawa kimia dalam penemuan obat modern. Docking molekuler memprediksi konformasi dan orientasi ligan di tempat pengikatan protein target. Hasil ikatan molekuler protein 2hi4 dengan 15 senyawa kimia menunjukkan bahwa tiga senyawa kimia memiliki tingkat energi pengikat terbaik, yaitu benzo(a)pyrene, pteryxine, dan quinine. Perbandingan asam amino yang dilihat dari visualisasi 2D menunjukkan bahwa terdapat 7 asam amino yang sama, yaitu ALA317, GLY316, ASP313, ASP320, PHE260, PHE226, dan THR118


Journal article

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