Molecular dynamics simulations of surfactant protein C mimic in phospholipid bilayers

CHED 1009

Wesley M. Smith, wmsmith@csupomona.edu1, Stephen M. Dutz, smdutz@csupomona.edu1, Patrick W. Mobley, pwmobley@csupomona.edu1, Larry M. Gordon, lgordon2@san.rr.com2, Frans J. Walther, fwalther@labiomed.org2, Alan J. Waring, awaring@mednet.ucla.edu3, and Shantanu Sharma, sks@csupomona.edu1. (1) Department of Chemistry and Center for Macromolecular Modeling & Materials Design (CM3D), California State Polytechnic University, Pomona, CA 91768, (2) L.A. Biomedical Research Institute, Harbor-UCLA Medical Center, Bldg. F5 South, 1124 West Carson Street, Torrance, CA 90502, (3) Department of Medicine, UCLA School of Medicine, Center for the Health Sciences, CHS-37-055, 10833 Le Conte Avenue, Los Angeles, CA 90095
Surfactant protein C (SP-C) is an exceptionally hydrophobic lipopeptide found in mammalian lung surfactant. Important SP-C functions include lipid bilayer interactions with the lung surface monolayer and modulation of the surfactant lipid viscosity. Previous 2D-NMR studies in organic solvents and our Fourier transform infrared (FTIR) measurements of SP-Cff in 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC) bilayers confirm the peptide is largely helical with its axis parallel to the long axis of the phospholipid acyl chains. Molecular dynamics (MD) simulations of SP-Cff in hydrated POPC bilayers reveal that the peptide maintains helical conformations in the polyvaline domain of SP-Cff for long time periods (100 nsec), with the helical axis oriented nearly perpendicular to the bilayer surface. Finally, the structures derived from MD simulations were validated by comparison with experimental lipid order parameters and the average area per lipid.