Peptide-membrane Interactions: Peptide Insertion and Induced Hole Formation Yonghua Deng & Guanghong Wei Department of Physics, Fudan University, Shanghai 200433, China Figure 2: Top view: water not showed protein in red, Lipid in cyan Figure 1: Side view: lipid not showed, P atoms in cyan, water in yellow ≈0.7 nm Initial:0 ns: the intact membrane, with pHLIP(α-helix) half inserted Final: 150ns: pHLIP fully in the membrane; Hole formed beside the pHLIP, as a water channel Figure 3: number of water molecules in the hole as a function of time Figure 4: Minimal cross-sectional area of hole as a function of time Conclusion 1.The pHLIP, when half inserted in the membrane, it can insert into the membrane rapidly. 2.In the acidic environment, pHLIP, when inserted in the membrane, can induce the membrane to form a stable water hole, but it cannot mechanically damage the membrane. 3.The results are important to understand the water channel and toxicity of proteins, and it demonstrate the possibility of using PHLIP as a new drug molecular cargo. References [1]Yana et al, Energetics of peptide (pHLIP) binding to and folding across a lipid bilayer membrane, PNAS, 105,40,2008 [2]Yana et al, Engleman, Translocation of molecules into cells by pH-dependent insertion of a transmembrane helix, PNAS, 103,17,2006 [3]Pieter E. S. et al, Induction of negative curvature as mechanism of cell toxicity by amyloidogenic peptides, JACS,131(12),4470,2009 -----Thank Yin Luo, Zhaoming Fu, Yan Lu, Huiyu Li, Yun Zhang, Zhongwen Chang for helpful discussion-----