Pitfalls in the use of the torsion angle driving method for the calculation of conformational interconversions

Several deficiencies and potential sources of error in the torsion angle driving method, the approach employed most frequently for the simulation of conformational interconversions, have been studied. A general explanation of the observed effects is given in terms of the energy surface and of the effects brought about by “side valleys.” Several examples of molecular mechanics calculations of conformational interconversions, among them the cyclohexane ring inversion, illustrate the problems.