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

Abstract

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.

Keywords:

• free energy
• carbohydrate ring pucker
• adaptive forces
• QM/MM
• FEARCF
• reaction coordinate

Acknowledgements

This work is based upon research supported by the South African Research Chairs Initiative (SARChI) of the Department of Science and Technology and the National Research Foundation (NRF) awarded to KJN. CB would like to thank fellow group member Johan Strümpfer for helpful discussions and the National Research Foundation (Pretoria) for PhD fellowship support. Kevin J. Naidoo is pleased to present this work in honour of Henry Fritz Schaefer's 65th birthday.