title: The effect of environment on the stability of an integral membrane helix: molecular dynamics simulations of surfactant protein C in chloroform, methanol and water.
abstract: A series of three molecular dynamics simulations at 300 K in explicit solvent environments of chloroform, methanol and water has been performed on the pulmonary surfactant lipoprotein, SP-C, comprising several consecutive valine residues in order to investigate the stability of the alpha-helical conformation. Two additional simulations were performed on truncated SP-C with a five-residue N-terminal deletion at 300 K and 500 K in water, the high temperature run in order to increase the rate of peptide denaturation. Indications of destabilization appear in chloroform during 1 ns while the SP-C alpha-helix is remarkably stable during 1 ns in methanol and water. In particular the polyvalyl part comprising residues Val15 to Val21 remains intact even at elevated temperature, and the valines do not disrupt the alpha-helical conformation. The valyl-rotamer sampling is partly restricted. Unfolding takes place successively along the primary sequence starting from the C-terminal end. Factors affecting polypeptide stability in molecular dynamics simulations are addressed. The intrinsic helix-forming tendency of valine residues and its dependence on the sequence context, and the role of the solvent environment in stabilizing or destabilizing an alpha-helical fold, are discussed.
authors.affiliation: Laboratory of Physical Chemistry, ETH-Zentrum CH-8092, Zürich, Switzerland.
authors.forename: H
authors.initials: H
authors.lastname: Kovacs
authors.forename: A E
authors.initials: AE
authors.lastname: Mark
authors.forename: J
authors.initials: J
authors.lastname: Johansson
authors.forename: W F
authors.initials: WF
authors.lastname: van Gunsteren
mesh_terms: D000595:Amino Acid Sequence; D002725:Chloroform / Q000737:chemistry*; D003198:Computer Simulation; D000432:Methanol / Q000737:chemistry*; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011510:Proteolipids / Q000737:chemistry*; D011663:Pulmonary Surfactants / Q000737:chemistry*; D012997:Solvents; D014867:Water / Q000737:chemistry*
chemical_list: D011510:Proteolipids; D011663:Pulmonary Surfactants; D012997:Solvents; D014867:Water; D002725:Chloroform; D000432:Methanol