Molecular docking of rat myostatin with human follistatin: an in-silico analysis

Myostatin (MSTN) belongs to transforming growth factor-beta (TGF- ) family as an autocrine/paracrine hormone produced mainly by muscle cells that inhibits muscle mass development. Follistatin is known to antagonize the function of TGF- ligands, such as MSTN and activin A. Therefore, the aim of this study was to predict the ۳D structure of rat (Rattus norvegicus) MSTN and investigate the interaction between rat MSTN and human (Homo sapiens) follistatin with molecular docking method. This method could provide insights into increase muscle mass in animals. The rat MSTN structure was predicted with Swiss-model server, and evaluated with SAVES ۶.۰ online server. Then, the interactions of rat MSTN with human follistatin (retrieved from UniProt: P۱۹۸۸۳) were performed using H-DOCK online server based on a hybrid algorithm of template-based modeling and abinitio free docking. The Verify۳D assessment of rat MSTN three-dimensional indicates that this protein having appropriate compatibility with ۱D and ۳D protein structures. ERRAT is an online server that could show incorrect regions of protein structures according to errors leading to random distributions of atoms, which can be distinguished from correct distributions. The ERRAT score for the predicted rat MSTN was ۸۰% which was in the acceptable range. The Ramachandran plot is the ۲d plot of the - torsion angles of the protein backbone that provided overall view of protein conformation. Ramachandran plot indicated that in the predicted rat MSTN, around ۸۰% residues belonged to the most favored regions. The docking result showed that human follistatin can be connected tightly to the predicted rat MSTN with a docking score of -۲۴۴.۷۳. Furthermore, the amino acids involved in the hydrogen bond including, H۳۲۴, H۳۲۶ and Y۳۲۲ with hydrogen bond distances of ۲.۷, ۳.۵ and ۱.۹, respectability. The results of this study indicated possible application of human follistatin to inhibit rat MSTN, although further molecular dynamics study in addition to in-vitro experiments are required.

کلیدواژه ها:

Follistatin ، Rattus norvegicus ، Myostatin ، Muscle ، Molecular Docking