THE EFFECT OF ENVIRONMENT ON THE STABILITY OF AN INTEGRAL MEMBRANE HELIX - MOLECULAR-DYNAMICS SIMULATIONS OF SURFACTANT PROTEIN-C IN CHLOROFORM, METHANOL AND WATER

A series of three molecular dynamics simulations at 300 K in explicit solvent environments of chloroform, methanol and water has been perfor med on the pulmonary surfactant lipoprotein, SP-C, comprising several consecutive valine residues in order to investigate the stability of t he alpha-helical conformation. Two additional simulations were perform ed 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 stabl e during 1 ns in methanol and water. In particular the polyvalyl part comprising residues Val15 to Val21 remains intact even at elevated tem perature, and the valines do not disrupt the alpha-helical conformatio n. The valyl-rotamer sampling is partly restricted. Unfolding takes pl ace successively along the primary sequence starting from the C-termin al end. Factors affecting polypeptide stability in molecular dynamics simulations are addressed. The intrinsic helix-forming tendency of val ine residues and its dependence on the sequence context, and the role of the solvent environment in stabilizing or destabilizing an alpha-he lical fold, are discussed.