PEMODELAN STRUKTUR PROTEIN RESEPTOR BETA-1 ADRENERGIK DENGAN METODE HOMOLOGY MODELLING

• Main Author: Bima Sakti, Andaru
• Format: Final Project
• Language: Indonesia
• Online Access: https://digilib.itb.ac.id/gdl/view/54484
• Institution: Institut Teknologi Bandung

Human beta-1 adrenergic receptor (B1AR) is an adrenergic receptor which has important role in the sympathetic nervous system. Rational drug development on ligands for this receptor was hard to be performed as until this study was conducted there was no three-dimensional structure of B1AR available. The structure had not been elucidated through experimental methods such as X-Ray Diffraction due to its instable properties. The aim of this study was to obtain three-dimentional structure of B1AR by homology modelling approach. Modelling process was conducted through several steps, such as protein template search, sequence alignment, model building, and validation which was followed by refinement and further validation. The protein target sequence was taken from the NCBI database with ascension number of NP_000675.1. Models were built using three webservers, namely SWISSMODEL, MODWEB, and I-Tasser, and 4 models were generated: SM1, SM2, WM1, and IT1. Validation process were performed using the following parameters: clashscore, Ramachandran outlier, Ramachandran favoured, Rama distribution z-score, dan QMEAN Z-score. SM2 was chosen to undergo the refinement process which was accomplished by using the GalaxyRefine program. Refined model SM2-R5 was the best model with the following values in validation: Ramachandran outlier 1,47% (1 outlier); Ramachandran favored 97,95%; Rama Distribution Z-score -0,10 ± 0,37; dan QMEAN Z-score -2,93. In conclusion, SM2-R5 was predicted to have the closest resemblance to the actual structure of B1AR protein.