Binding of Tat peptides on DOPC and DOPG lipid bilayer membrane studied by molecular dynamics simulations

Cell-penetrating peptides (CPPs) have an ability of internalisation to inner cells through plasma membrane. The plasma membrane and lipid bilayer in experiments contain negatively charged lipids. HIV-1 Tat peptide, which is one of the CPPs, has many arginines with positive charge, and strongly interacts with negatively charged lipids. We investigate the difference between neutral lipids, 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), and negatively charged lipids, 1,2-dioleoyl-sn-glycero-3[phospho-rac-(1-glycerol)] (DOPG), by all-atom molecular dynamics simulations. We found that the speed of binding of Tat to lipid membrane for DOPC is more than 10 times faster than the speed for DOPG. The Tat peptides bind to the lipid membrane by attractive interaction between arginine in Tat and phosphates in lipids. Comparing the number of phosphates binding to arginine, DOPG gives a larger number than DOPC. The differences indicate the importance of negatively charged lipids for the investigation of the property of CPPs.