Fancui Meng

Structural effects and translocation of spontaneous membrane-translocating peptides with POPC bilayer

Martini coarse-grained force field simulations have been carried out to estimate the free energy profiles of the spontaneous membrane-translocating peptide TP2 and one negative control peptide ONEG with POPC as the model bilayer. The results show that the free energy minimum of TP2 is −20kJ/mol lower than that of ONEG. In addition, the minimum of TP2 shifts slightly to the bilayer center compared with ONEG. The translocation barrier height for TP2 and ONEG are 119.0kJ/mol and 155.7kJ/mol, respectively. The lower central energy barrier of TP2 facilitates the transition between two leaflets of POPC. Both translocating peptides induce the formation of funnel-shaped structures at the bilayer center, but TP2 has a more compact structure and brings less perturbation compared with ONEG. Subsequently all atom molecular simulations testify the findings. It is indicated that compared with its negative control ONEG, TP2 binds better with lipid and penetrates deeper into bilayer with less perturbation to the bilayer structure. Our findings may shed light on the design and virtual screening of spontaneous membrane-translocating peptides.