Free Energies from Adaptive Reaction Coordinate Forces (FEARCF): an application to ring puckering

Previously an adaptive reaction coordinate force biasing method based on probability distributions has been used to calculate the free energy of conformation, configuration and chemical reactions. This method has recently been generalised to perform calculations on multidimensional reaction coordinates. This paper presents details of this method, termed Free Energies from Adaptive Reaction Coordinate Forces (FEARCF). The efficiency of sampling of this method is demonstrated by applying it to the problem of sampling the many characteristic pucker conformations of a β-D-glucose pyranose using a semi-empirical PM3 Hamiltonian. The sampling ratio of the global minimum conformer (4C1) to the highest energy conformer (a planar hexapyranose ring) is 1.7:1. Pucker free energy surfaces such as the one presented here can be a useful tool in the analysis of enzymatic reactions involving molecular ring puckers in the Michaelis complex.