Conformational equilibria of terminally blocked single amino acids at
the water-hexane interface.
A molecular dynamics study
C. Chipot and A. Pohorille, J. Phys. Chem., 102 281-290 (1997).
Abstract:
The conformational equilibria of the Ac- and -NHMe terminally blocked L-alanine,
L-leucine and L-glutamine
amino acids have been examined in vacuum, bulk water and at the water-hexane interface,
using multi-nanosecond molecular dynamics simulations. Two-dimensional probability
distribution functions of finding the peptides at different backbone dihedral angles and were calculated and free energy differences
between different conformational states were determined. All three peptides are
interfacially active, i.e. tend to accumulate at the interface. Conformational
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 peptides. Conformational preferences in the interfacial environment,
arise from the interplay between the electrostatic and hydrophobic effects. As in aqueous
solution, electrostatic solute-solvent interactions lead to the stabilization of more
polar peptide conformations. The hydrophobic effect is manifested at the interface by a
tendency to segregate polar and nonpolar moities of the solute into the aqueous and the
hexane phases, respectively. For the terminally blocked glutamine, this favors
conformations, for which such a segregation is compatible with the formation of strong,
backbone-side chain intramolecular hydrogen bonds on the hexane side of the interface. The
influence of the hydrophobic effect can be also noted in orientational preferences of the
peptides at the interface. The terminally blocked leucine is oriented such that its
nonpolar side chain is buried in hexane, whereas the polar side chain of glutamine is
immersed in water. The free energy of rotating the peptides along the axis parallel to the
interface by more than 90
is substantial. This indicates that peptide folding at interfaces is strongly driven by
the tendency to adopt amphiphilic structures.
and 
were calculated and free energy differences
between different conformational states were determined. All three peptides are
interfacially active, i.e. tend to accumulate at the interface. Conformational
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 peptides. Conformational preferences in the interfacial environment,
arise from the interplay between the electrostatic and hydrophobic effects. As in aqueous
solution, electrostatic solute-solvent interactions lead to the stabilization of more
polar peptide conformations. The hydrophobic effect is manifested at the interface by a
tendency to segregate polar and nonpolar moities of the solute into the aqueous and the
hexane phases, respectively. For the terminally blocked glutamine, this favors
conformations, for which such a segregation is compatible with the formation of strong,
backbone-side chain intramolecular hydrogen bonds on the hexane side of the interface. The
influence of the hydrophobic effect can be also noted in orientational preferences of the
peptides at the interface. The terminally blocked leucine is oriented such that its
nonpolar side chain is buried in hexane, whereas the polar side chain of glutamine is
immersed in water. The free energy of rotating the peptides along the axis parallel to the
interface by more than 90
is substantial. This indicates that peptide folding at interfaces is strongly driven by
the tendency to adopt amphiphilic structures.