Pemodelan In Silico Inhibitor Gsk-3β (CHIR99021, CHIR98014, AZD1080, TWS11) Dan Turunan Zerumbon Terhadap Protein 4PTG Melalui Perangkat Lunak PYR

Abstract

Glycogen synthase kinase-3 (GSK-3) is a serine / threonine kinase whose activity is related to various diseases such as diabetes, cancer, Alzheimer's, and stroke. In silico method is one of the choice to study and look for GSK-3 inhibitor compounds that are potent, selective, and has the potential to be developed as a drug. There are four reported compounds that have potential as an inhibitors of GSK-3, namely CHIR99021, CHIR98014, AZD1080 and TWS119, along with 40 dataset compounds, 50 decoys and derived molecules from zerumbon as novel compounds used for molecular docking run by a laptop (Toshiba PICO DJV with specifications:Intel® Atom™ N280 1GB RAM , OS Windows 7 32 bit), target protein and the native ligand were prepared using Chimera and then converted from 2D into 3D structures with Marvin. Docking proceed with Autodock and Vina method (PyRx). Results are visualized with PyMOL and PLIP. CHIR99021, CHIR98014 and AZD1080 are a selective inhibitor of GSK-3 isoforms α and β. TWS119 is a selective inhibitor of GSK-3 β isoforms belong to pyrrolopyrimidine groups. PyRx results showed that from 4 potentially reported compound, one of them (CHIR98014) is not better than the native ligand with binding affinity only 13.11%. Novel compounds (ZER08) with binding affinity of 99.8% compared to the dataset is considered as a potential compound to be tested further in laboratory as an anti-diabetes with mechanism as GSK-3 isoform βinhibitor.