Peptide Isomerization is Suppressed at the Air-Water Interface.

We use molecular dynamics simulations to study the thermodynamics and kinetics of alanine dipeptide isomerization at the air-water interface. Thermodynamically, we find an affinity of the dipeptide to the interface. This affinity arises from stabilizing intramolecular interactions that become unshielded as the dipeptide is desolvated. Kinetically, we consider the rate of transitions between the α and β conformations of alanine dipeptide and evaluate it as a continuous function of the distance from the interface using a recent extension of transition path sampling, TPS+U. The rate of isomerization at the Gibbs dividing surface is suppressed relative to the bulk by a factor of 3. Examination of the ensemble of transition states elucidates the role of solvent degrees of freedom in mediating favorable intramolecular interactions along the reaction pathway of isomerization. Near the air-water interface, water is less effective at mediating these intramolecular interactions.