Prediction of potential stabilizer mutation of Interferon beta 1 A (Cinovex) via molecular dynamics simulation

Iranian drug CinnoVex (Interferon beta) is an important drug for preventing the progress of M.S. disease and increase of its stability is very important. In this research, we designed five mutations in the structure of interferon and performed molecular dynamics simulation and docking and the best stabilizer mutation was determined. At first, the wild type structure of beta interferon was subjected to Pop music server for prediction of stabilizer mutations. Then the first four proper score mutations were selected and mutated structures and a mix mutation (mut 2+ mut 3) (mut 5) were made. Then, molecular dynamics simulation performed via Gromacs 5 package on wild and mutated structures in five temperatures (300, 350, 400, 450, 500 K) separately for 20 ns (in total 600 ns). The simulation parameters were calculated in each temperature for all structures during the last 10 ns of simulations. The plots of temperature against averages of parameters were drawn and the regression slope of parameters was calculated to find the more stable structure. The results revealed that mutation 3 (G127E) is the best mutation compare to wild interferon. Also, the binding power of mutation 3 with its receptor is more than wild type and other mutations. It seems that the increase of hydrophilicity of protein around position 127 in mutation 3 on interferon surface leads to increase the stability and solubility of it ex vivo.