An expression for the transition state theory rate constant is provided in terms of the potential of mean force for a general reaction coordinate and the mass-weighted gradient of this reaction coordinate. The form of the rate constant enables the straightforward calculation of rates for infrequent events with conventional umbrella sampling and free energy perturbation methods. The approach is illustrated by an application to hydride transfer in the enzyme dihydrofolate reductase using a hybrid quantum/classical molecular dynamics method. Inclusion of the nuclear quantum effects of the transferring hydrogen increases the transition state theory rate constant by a factor of 244. (c) 2005 Elsevier B.V. All rights reserved.