A formalism is given for predicting reactivity of complex systems by combining electronic structure calculations with forcefield calculations within a transition state theory framework. The theory is employed in combination with the Fukui function to produce a simulation method capable of the ensemble sampling needed to examine sterically complex systems. An important linkage between reactivity information and energetic quantities is provided by introduction of the Fukui overlap integral. This spatial overlap integral measures the coincidence of electron donating regions on a nucleophile with electron accepting regions on the corresponding electrophilic reactant. We show that configurations with high values of this overlap integral tend to have lower density-functional theory energies. Thus, Fukui functions calculated once on single isolated reactants can be used to quickly estimate the reactivity of configurations generated using conventional forcefield-based simulations. The correlation between energies and high overlap integrals can also be used to identify initial guess configurations for transition state searches. However, in the present implementation, real transition states are not accessible because intramolecular geometry relaxation is not allowed. The proposed method is tested on electrophilic aromatic alkylation reactions. Simulation results successfully reproduce experimental substituent effects in a series of variously substituted aromatics. Especially encouraging is the ability of the simulations to predict steric effects in the reaction of toluene with a series of electrophiles of varying bulkiness. Further applications, previously inaccessible to simulation, are expected in systems where steric effects play a dominant role in determining reaction selectivity. (C) 2001 American Institute of Physics.