Kinetics and reaction coordinate for the isomerization of alanine dipeptide by a forward flux sampling protocol

Forward flux sampling (FFS) simulations were used to study the kinetics of alanine dipeptide both in vacuum and in explicit solvent. The recently proposed FFS least-squares estimation approach and an algorithm that optimizes the position of the interfaces were implemented to determine a reaction coordinate that adequately describes the transition dynamics. A new method is also introduced to try to ensure that the ensemble of "starting points" (for the trial trajectories) is properly sampled. The rate constant estimates for the C7(eq)-->C5 transition of alanine dipeptide in vacuum were used to demonstrate the consistency between Monte Carlo and molecular dynamics (MD) simulations. FFS-MD simulations were then performed for the study of the beta(2)/alpha(R)-->C5/C7(eq) transition in explicit solvent. The kinetic results for both systems in vacuum and explicit solvent are in general agreement with previous experimental and computational studies for this peptide. In vacuum, an additional dihedral angle besides the one typically used as order parameter is identified as a significant variable in the reaction coordinate model. In solution, several dihedral angles and variables that describe the solvent action on the molecule's dynamics are found to play a significant role in the description of the system's dynamics.