Monte Carlo and molecular dynamics studies of peptide-membrane binding

Monte Carlo (MC) and molecular dynamics (MD) simulations have been used to investigate the binding of sandostatin (an 8 residue cyclic peptide) to a neutral POPC bilayer. From the Monte Carlo simulations, in which ionic strength is treated explicitly through the inclusion of ions, the electrostatic contribution to the binding free energy is obtained. In the MD simulations, the peptide is initially placed in a region of bulk water density and allowed to spontaneously bind to the bilayer surface within 2 nanoseconds (ns). Following deprotonation of the peptide N-terminus, sandostatin penetrates more deeply into the bilayer interior. Excellent agreement was found for details of the simulated complexes and those measured by experiment. The partitioning of the amino acid side chains into the bilayer interface agrees with an experimentally determined hydrophobicity scale.