An adaptive umbrella sampling procedure in conformational analysis using molecular dynamics and its application to glycol

A novel way has been developed for using the umbrella potential method of calculating the potential of mean force using molecular dynamics. During a simulation, the umbrella potential is improved periodically, taking into account all results obtained previously. The method was tested by the determination of the potential of mean force for the central dihedral angle in glycol (as a molecule in vacuo and in solutions in water and in CCl4). Advantages over other methods are that a relatively small amount of manual intervention is necessary and that an intermediate result after a small simulation time is already a complete, although crude estimate of the potential of mean force. A robust method to estimate the error in obtained energy differences between conformations and in the parameters of the potential of mean force (PMF) is also supplied.