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Transcript
Peptide-membrane Interactions: Peptide Insertion and Induced Hole Formation Y. Deng & G. H. Wei Department of Physics, Fudan University, Shanghai 200433, China Abstract: The pH low-insertion peptide(pHLIP) serves as a model system for peptide insertion and folding across a lipid bilayer. Under pH-low environment, it inserts across the bilayer as an α-helix. Recent experimental studies show that it may prove a promising tool for selective delivery agents for drug therapy. However, the mechanism by which the pHLIP influence the bilayer is poorly understood. Here we use all atomistic molecular dynamics simulation to explore the interaction between the pHLIP and the model membrane bilayer 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC). The pHLIP rapidly attaches to the surface of the POPC and rests there for a long time. However, if it breaks through the energy barrier of the surface, it rapidly inserts into the bilayer and, surprisingly, it induces the membrane to form a 0.5-2 ns hole parallel to the inserted PHLIP, across which the water permeates. This hole may permits other proteins or small molecules to go across. The pHLIP disrupts the membrane with a permeating hole but it doesn’t ruins the membrane. Results are important to understand the toxicity of the proteins and demonstrate the possibility of using pHLIP as a new drug molecular cargo, which we believe will be useful in a variety of biochemical and biophysical investigations related to the cell membrane and drug design. Keywords: pHLIP, membrane protein, protein insertion, hole formation, drug delivery