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.