The effect of orientation dynamics in melittin as antimicrobial peptide in lipid bilayer calculated by free energy method

Melittin is a widely studied antimicrobial peptide which has gained interest because of its potential in therapeutic use. To perform its antimicrobial function, the melittin prefer to be in a certain state of membrane. In this study, we simulate the melittin in horizontal orientation towards the surface of membrane and in vertical orientation inside transmembrane state. The free energies are then calculated to asses the most favorable orientation, indicating its stable structure, of this peptide interacting with the lipid bilayer. Umbrella sampling with and without pulling simulations is carried out to obtain the sampling windows which used in observing the free energy changes along the reaction coordinate. From our simulations, we found that melittin in vertical orientation in transmembrane state has smaller free energy value than the horizontal one indicating that melittin is more favorable in this configuration. Our results show that melittin undergoes reorientation process from horizontal to vertical to perform its antimicrobial function.