Membrane insertion peptides have been developed in recent years and serve as cargos to deliver small molecules into cells. A class of membrane insertion peptides is the so called pH-induced peptides (pHLIPs), which are able to insert into membrane when the environment pH is acidic. Despite a number of experimental studies, the insertion process as well as the penetration mechanism is still worth study with computational methods. Thus, we performed molecular dynamics simulations in this study to elucidate the detailed penetration process and mechanism. Both protonated and unprotonated peptides are employed to interact with a POPCs bilayer. By analyzing the trajectory of the simulation, the peptide travelling across membrane is expected to take milliseconds or seconds. While the peptide penetrating through the POPC bilayer boundary is much faster (several nanoseconds). More importantly, the elaborate energies between a peptide and water molecules, the energies between a peptide and POPCs have been analyzed throughout the simulation time correspondingly. A constant decrease of interaction energies have been observed for peptide-water interaction in the protonated condition. At last, we employ the statistics of hydrogen bonds to explain the penetration mechanism tentatively. For the protonated system, the decrease of hydrogen bonds of peptide-water and the increase of hydrogen bonds of peptide- POPCs have been considered as the main driven force for the peptide insertion.
Keywords: Molecular dynamics, pH-induced, peptide insertion, POPC.