همایش ملی بیوانفورماتیک ایران

صفحه اصلی / 4th international edition and 13th Iranian Conference on Bioinformatics

Molecular docking and bioinformatics study of active compounds of thyme) Thymus vulgaris( in inhibiting COX-2 enzyme related to inflammatory diseases

نویسندگان :

Razieh Biglari Farash¹ Azizollah Kheiry² Najmaddin Mortazavi³ Mohsen Sani khani⁴

1- دانشگاه زنجان 2- دانشگاه زنجان 3- دانشگاه زنجان 4- دانشگاه زنجان

کلمات کلیدی :

thyme،molecular binding،bioinformatics،prostaglandin

چکیده :

Inflammation is a natural response of the body to injury or infection that, if chronic, can lead to diseases such as rheumatoid arthritis, cancer, and heart disease. The cyclooxygenase-2 enzyme plays a key role in the production of prostaglandins and inflammatory processes, and its inhibition is recognized as a therapeutic target. Molecular docking is a method often used in drug design because it can predict how small molecule ligands will bind to target binding sites. Molecular docking can be used to identify potential compounds that inhibit the COX-2 enzyme. thyme )Thymus vulgaris( has proven anti-inflammatory effects with its bioactive compounds such as thymol, carvacrol, and linalool. In this study, bioinformatics methods including molecular docking and molecular dynamics simulations were used to investigate the interaction of these compounds with COX-2. Initially, information related to thymol and carvacrol was extracted from the PubChem database (PubChem Database, 2024). The crystal structure of the COX-2 enzyme was obtained from the Protein Data Bank (Protein Data Bank, 2024). AutoDock Vina software was used for docking simulation (Trott and Olson, 2010). The compounds were placed in the active site of COX-2 and their binding energies were calculated. GROMACS software was used for dynamic simulation. The stability of the complexes was evaluated by indices such as the difference between the crystal structure of the ligand compound and the predicted binding (RMSD) and kinetic energy. The pharmacokinetic properties and toxicity of the compounds were predicted using the SwissADME tool. The docking results showed that carvacrol has a lower binding energy than thymol, indicating its stronger interaction with the COX-2 active site. The hydrogen bond binding energy of thymol with the active site of the COX-2 enzyme was negative 8.6 kcal/mol, while the binding energy of carvacrol was negative 1.7 kcal/mol, making this compound a better option than thymol for pharmaceutical use. The RMSD of the thymol-COX-2 and carvacrol-COX-2 complexes were about 1.2 and 1.8 Å, respectively, indicating the high stability of these interactions during the 50 ns simulation. Kinetic energy changes of the compounds also showed that the carvacrol complex is more stable. Drug absorption, distribution, metabolism and excretion (ADMET) analysis (Dhanaraj and Asok, 2017) showed that carvacrol has high permeability through the blood-brain barrier (BBB) and thymol has lower permeability, making carvacrol a potential candidate for the treatment of nervous system inflammation. This study showed that the carvacrol compound from Shiraz thyme plant interacts strongly with the COX-2 enzyme and can be investigated as a drug candidate for inhibiting this enzyme. Molecular dynamics simulation and ADMET analysis showed low hepatotoxicity for both compounds, confirming the stability and safety of these compounds. It is suggested that further experimental tests be performed to confirm these results.