Role of N-acetylserotonin O-methyltransferase in bipolar disorders and its dynamics

Abstract

N-Acetylserotonin O-methyltransferase (ASMT), despite having medical significance and structural complexity, has not been explored at any level yet and thus, it is a topic of extensive research. Comparative modeling helped in building the structures. Comparative modeling has been tweaked at various levels and different computational tools were employed to explore the proteins at residual level. ASMT was constructed through MODELLER, minimized by using different force field and then active site determination has been carried out. Production run of 10ns is done and the time dependant behavior of protein on different timescales has been noticed through root mean square deviation (RMSD) and root mean square fluctuation (RMSF). Results from ASMT yielded that the RMSD values have fluctuated and remained stable afterwards. These findings suggest that first hundred residues are responsible for the structurally and dynamically abnormal behavior of ASMT. RMSF values obtained through simulation were also consistent with these findings and a unique structure with first hundred residues, more flexible than the rest of structure, is observed for the first time in ASMT. This can also provide a new basis for the interpretation of catalytic and pharmacological properties with mechanistic explanation for this protein.