A method for the direct conversion of quantum mechanical atoms within a free energy perturbation calculation is presented. The only constraint on the identity of the perturbed atoms is that they contain the same number of valence electrons and that they are parametrized within PM3, AM1, or MNDO. The interconversion of atom types is done in the context of a semiempirical/molecular mechanical coupled potential. This allows a large system to be examined at a relatively modest computational expense while maintaining a quantum mechanical model of the portion of the system which is of particular interest (an enzyme active site for example). To demonstrate the efficiency of the method, simulations for the conversion of chloride to fluoride and ammonium to methane, in aqueous solution, are presented. The methods described herein can be readily extended to ab initio methods.