Potensi Molecular Docking Protein Antigen 85 (Ag85) Kompleks Mycobacterium Tuberculosis Terhadap Integrin β2, β3, dan α5β1 Sebagai Pengembangan Vaksin Tuberkulosis Berbasis Protein Sekretori

Abstract

Tuberculosis is a chronic infectious disease caused by the bacteria Mycobacterium tuberculosis (M. tuberculosis). Bacille Calmette-Guerin (BCG) is still the only type of tuberculosis (TB) vaccine recognized by the World Health Organization (WHO). The BCG vaccine has limited protection and is a weakened vaccine that carries a high risk of becoming malignant. Therefore, there is still a need for a better vaccine to prevent TB transmission. The vaccines currently being developed can be derived from the secretory protein of a pathogen. One of the secretory proteins found in M. tuberculosis is the Ag85 complex which has three kinds of proteins, namely Ag85 A, Ag85 B, and Ag85 C. Proteins Ag85 complex binds to integrin receptors in M. tuberculosis virulence. Integrins that work in bacterial migration, activities and trigger protein recruitment, and strengthen cell adhesion are integrins β2, β3, and α5β1. Therefore, this study aims to determine the potential for binding between the complex Ag85 protein and the integrin receptors β2, β3, and α5β1 as an in silico development of a secretory protein-based TB vaccine. This research is exploratory research with in silico testing using the molecular docking method. Molecular docking was carried out on the ClusPro website which was based on the binding energy values and the resulting binding interaction models. The structures of the Ag85 protein complex and integrin β2, β3, and α5β1 were obtained via the Protein Data Bank (PDB) website and the binding interaction model was visualized using PyMOL software. In this study, the binding energy values obtained for the nine bonds between the Ag85 A, B, and C proteins with integrins β2, β3, and α5β1 were negative and all hydrogen bonds showed that the bonds formed were strong and stable. The lowest binding energy value of the Ag85 A protein with β2 integrin is -1036.0, the lowest binding energy value of the Ag85 B protein with β2 integrin is -1055.0, the lowest binding energy value of the Ag85 C protein with β2 integrin is -962.0, value The lowest binding energy value of the Ag85 A protein with β3 integrin is -1007.4, the lowest binding energy value of the Ag85 B protein with β3 integrin is -904.5, the lowest binding energy value of the Ag85 C protein with β3 integrin is -1004.1, the lowest binding energy value of the protein Ag85 A with integrin α5β1 is - 987.9, the lowest binding energy value of the Ag85 B protein with integrin α5β1 is -931.1, the lowest binding energy value of the Ag85 C protein with integrin α5β1 is -935.1. The lowest binding energy value among the nine bonds is shown in the bond between the Ag85 B protein and integrin β2, namely -1055.0. The conclusion of this study, conducted in silico, proves that the Ag85 protein complex can bind to integrins β2, β3, and α5β1. The bonds formed are all hydrogen bonds with binding energy of all bonds of negative value and the distance of all bonds <3Å which indicates a strong and stable bond so that it has the potential as a candidate antigen for TB vaccine development. The bonds formed between Ag85 A, Ag85 B with integrin β2, Ag85 A with integrin β3, and Ag85 A, Ag85 B, Ag85 C with integrin α5β1 are on the active side of amino acid residues. The interaction between the Ag85 complex with integrin α5β1 is the most bonds on the active side of amino acids, namely 10 active amino acid residues and has the most potential as a TB vaccine antigen candidate.