CONFORMATIONAL EQUILIBRIA OF TERMINALLY BLOCKED SINGLE AMINO-ACIDS ATTHE WATER-HEXANE INTERFACE - A MOLECULAR-DYNAMICS STUDY

The conformational equilibria of the acetyl and methyl amide terminall y blocked L-alanine, L-leucine and L-glutamine amino acids are examine d in vacuum, in bulk water, and at the water-hexane interface, using m ulti-nanosecond molecular dynamics simulations. The two-dimensional pr obability distribution functions of finding the peptides at different dihedral angles of the backbone, phi and psi, are calculated, and free energy differences between different conformational states are determ ined. All three peptides are interfacially active, i.e. tend to accumu late at the interface even though they are not amphiphilic. Conformati onal states stable in both gas phase and water are also stable in the interfacial environment. Their populations, however, cannot be simply predicted from the knowledge of conformational equilibria in the bulk phases, indicating that the interface exerts a unique effect on the pe ptides. Conformational preferences in the interfacial environment aris e from the interplay between electrostatic and hydrophobic effects. As in an aqueous solution, electrostatic solute-solvent interactions lea d to the stabilization of more polar peptide conformations. The hydrop hobic effect is manifested at the interface by a tendency to segregate polar and nonpolar moieties of the solute into the aqueous and the he xane phases, respectively. For the terminally blocked glutamine, this favors conformations for which such a segregation is compatible with t he formation of strong, backbone-side chain intramolecular hydrogen bo nds on the hexane side of the interface. The influence of the hydropho bic effect can be also noted in the orientational preferences of the p eptides at the interface. The terminally blocked leucine is oriented s uch that its nonpolar side chain is buried in hexane, whereas the pola r side chain of glutamine is immersed in water. The free energies of r otating the peptides along the axis parallel to the interface by more than 90 degrees are substantial. This indicates that peptide folding a t interfaces is strongly driven by the tendency to adopt amphiphilic s tructures.