KAJIAN INTERAKSI SENYAWA ANTIPSIKOTIK ARIPIPRAZOL DENGAN RESEPTOR DOPAMIN D3 MENGGUNAKAN METODE SIMULASI DINAMIKA MOLEKULAR

PUJI BUDI ASIH, Dr.rer.nat Ria Armunanto, M.Si

2015 | Skripsi | S1 KIMIA

Kajian interaksi senyawa aripiprazol dengan reseptor protein dopamin D3 menggunakan simulasi dinamika molekular telah dilakukan. Tujuan dari penelitian ini untuk mengetahui kelarutan ligan (aripiprazol dan ETQ) dalam air, dan interaksi komplek dopamin D3-aripirprazol. Penelitian diawali dengan proses docking ligan aripirazol berdasarkan binding site hasil docking ligan ETQ (eticopride) pada reseptor. Berdasarkan konformasi terbaik hasil docking ligan dilakukan simulasi dinamika molekuler free energy pertubation (FEP) untuk memprediksi energi solvasi ligan dan simulasi dinamik dopamin D3-aripirprazol pada kondisi NPT (number, pressure, temperature) tetap. Hasil penelitian menunjukkan energi solvasi aripirazol (-233,82 plus minus 0,89 kJ/mol) dalam pelarut air lebih rendah dibanding ligan ETQ (-181.98 plus minus 3,19 kJ/mol) dalam air. Hal ini menunjukkan bahwa kelarutan aripiprazol dalam air lebih besar dibanding dengan ETQ. Dalam kondisi NPT 500-600 ps terekam maksimal terjadi 6 ikatan hidrogen ETQ dengan pelarut, dan 7 ikatan hidrogen aripiprazol pelarut. Hasil docking aripiprazol memiliki ikatan hidrogen berjumlah 3 dengan residu asam amino yaitu asam aspartat (Asp79 O middle dot middle dot middle dot H-N5), tirosin (Tyr5 H middle dot middle dot middle dot O=C30), treonin (Thr392 H middle dot middle dot middle dot O=C30). Hasil simulasi dinamik dopamin D3-aripirprazol dapat membentuk 5 ikatan hidrogen dengan berinteraksi dengan residu asam amino : asam aspartat (Asp79 O middle dot middle dot middle dot H-N5), tirosin (Tyr5 H middle dot middle dot middle dot O=C30 dan Tyr5 O middle dot middle dot middle dot H-N7), treonin (Thr392 H middle dot middle dot middle dot O=C30) dan sistein (Cys83 H middle dot middle dot middle dot N6).

Study on interaction between aripiprazole with D3 Dopamin receptor using molecular dynamics simulation had been performed. The purpose of this study are to know solubility of ligands (aripiprazole and ETQ) in water, and interaction of D3 dopamine-aripiprazole complex. Firstly, docking of aripirazole to d3 dopamine receptor was performed based on ETQ apostrophe s binding site. The best conformation of ligand docking used to perform molecular dynamics simulation-free energy pertubation to predict solvation energy of ligands and dynamics simulation of D3 dopamine-aripiprazole complex in constant NPT (number, pressure, temperature). The result showed that solvation energy of aripiprazole (-233,82 plus minus 0,89 ) was lower than ETQ (-181.98 plus minus 3,19 kJ/mol) in water. It showed that solubility of aripiprazole was higher than ETQ in water. In 500-600 ps of simulation recorded that ETQ maximum could make 6 hydrogen bonds with water and aripiprazole maximum could make 7 hydrogen bonds with water. Docking apostrophe s result showed that aripiprazole could make 3 hydrogen bonds with 3 amino acid residues : aspartad acid (Asp79 O middle dot middle dot middle dot H-N5), tyrosine (Tyr5 H middle dot middle dot middle dot O=C30) and threonine (Thr392 H middle dot middle dot middle dot O=C30). Dynamics simulation apostrophe s result showed that aripiprazole could make 5 hydrogen bonds with amino acid residues : aspartad acid (Asp79 O middle dot middle dot middle dot H-N5), tyrosine(Tyr5 H middle dot middle dot middle dot O=C30 and Tyr5 O middle dot middle dot middle dot H-N7), threonine (Thr392 H middle dot middle dot middle dot O=C30) dan cysteine (Cys83 H middle dot middle dot middle dot N6).

Kata Kunci : aripiprazol, reseptor D3 dopamin, simulasi dinamika molekuler