THE COMPUTATION OF A POTENTIAL OF MEAN FORCE - CHOICE OF THE BIASING POTENTIAL IN THE UMBRELLA SAMPLING TECHNIQUE

Generally, the conformational equilibrium of flexible molecules change s upon solvation. The equilibrium distribution of conformers is determ ined by the potential of mean force for the relevant degrees of freedo m. However, the determination of the potential of mean force by straig htforward computer simulation is often impracticable owing to the pres ence of large energy barriers which prevent efficient sampling. A freq uently chosen technique to overcome the problems associated with such barriers is the umbrella sampling technique. Using molecular dynamics simulation of 1,2-dichloroethane solvated in water as a model case, we have investigated the influence of the choice of the biasing potentia l in the umbrella sampling technique on the computation of the dihedra l angle potential of mean force. The efficiencies of one- and multiple -window techniques are compared. For short simulation periods (25 ps) the latter technique performs better than the former. For longer simul ation periods the performance difference is obscured by fluctuations c aused by insufficient sampling of other slow processes occurring in th e system, induced by the anisotropy of the periodic boundary condition s.