Molecular-dynamics simulation of galanin in aqueous and nonaqueous solutionMolecular-dynamics simulation of galanin in aqueous and nonaqueous solution
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences. Pharmacy
1992Washington, D.C., 1992
Journal of the American Chemical Society. - Washington, D.C.
114(1992):11, p. 4028-4035
In order to increase our knowledge about the 29-residue-long neuropeptide galanin, computer simulations were carried out. As is the case with many other small peptides, galanin has nearly no secondary structure in water, unlike the situation when solvated in 2,2,2-trifluoroethanol. The galanin peptide was therefore subjected to periodic boundary molecular dynamics simulations with explicit treatment of solvent. One simulation in water (220 ps) and one simulation in 2,2,2-trifluoroethanol (120 ps) were carried out. In both cases the initial conformation was the structure, in 2,2,2-trifluoroethanol, as determined with NMR techniques (Wennerberg, A. B. A.; et al. Biochem. Biophys. Res. Commun. 1990, 166, 1102-1109). A very different behavior was observed in these different environments: the peptide remained stable in 2,2,2-trifluoroethanol while in the aqueous solution progressive unfolding of the C-terminal domain took place. The stability of the peptide in 2,2,2-trifluoroethanol validates the original structure determination. In addition, as a control experiment, the simulation points to the unique role of the water molecules in promoting the unfolding of the galanin molecule. In both simulations the probability of finding i-i + 3 hydrogen bonds was increased at the helix termini. The conformational changes occurring in the H2O simulation were studied in more detail, and 3(10)-type helices, or the presence of i-i + 3 hydrogen bonds, were detected during the unfolding. Water molecules thus replace the backbone hydrogen bonds during the unfolding, but this does not require the insertion of a "single" water molecule, as the analysis showed that different water molecules can pair up with the original atoms involved in the backbone hydrogen bond. Other observations point to the importance of side chain-side chain and side chain-main chain interactions during the unfolding process, giving each transition its specific characteristics. In conclusion these results show that molecular dynamics simulations allow, at least qualitatively, the study of solvent effects on peptide structure and folding.