Docking Dan Virtual Screening Senyawa Aktif Tanaman Obat Sebagai Inhibitor Tuberkulosis

Abstract

Tuberkulosis menjadi masalah kesehatan global saat ini. Mutasi pada protein enoyl-acyl carrier protein reductase (InhA) pada bakteri mycobacterium tuberculosis, menyebabkan resistensi terhadap obat yaitu isoniazid. Dalam penelitian ini, struktur tiga dimensi dari InhA sebanyak 10 protein wild-type dan 7 mutan dilakukan proses re-docking dan cross-docking terhadap ligan co-crystal. Dari proses tersebut, struktur PDB 4OIM, 5MTR, 4D0S, 2X23, 4TRJ, 3FNE, 4BQP, dan 4OXK untuk wild-type dan 5COQ, 5CP8, DAN 5OIF untuk protein mutan merupakan struktur yang memiliki nilai afinitas pengikatan terbaik dan RMSD <2,0 Å. Hasil cross-docking menghasilkan kode ligan XTO merupakan ligan stabil ketika berikatan dengan struktur wild-type dan mutan. Virtual screening menghasilkan ligan yang berasal dari senyawa aktif p-coumaroyltyramine, alpha- tocopherol atau vitamin e, apigenin 7-glucuronide dan cinnamamide memiliki potensi sebagai anti tuberkulosis berdasarkan hasil docking dan uji toksisitas.

Tuberculosis is a global health problem today. Mutations in the enoyl-acyl carrier protein reductase (InhA) protein in mycobacterium tuberculosis bacteria cause resistance to the drug, namely isoniazid. In this study, the three-dimensional structures of InhA for 10 wild-type proteins and 7 mutants were carried out by re-docking and cross-docking processes against co-crystal ligands. From this process, the PDB structures 4OIM, 5MTR, 4D0S, 2X23, 4TRJ, 3FNE, 4BQP, and 4OXK for the wild-type and 5COQ, 5CP8, AND 5OIF for the mutant protein are the structures that have the best binding affinity values and RMSD <2,0 Å. The results of cross-docking show that XTO is a stable ligand when bound to wild-type and mutant structures. Virtual screening produces ligands derived from the active compounds p-coumaroyltyramine, alpha-tocopherol or vitamin e, apigenin 7-glucuronide, and cinnamamide which have potential as anti tuberculosis based on the results of docking and toxicity tests.