This review considers the advances made in using computer simulations to el
ucidate the catalytic power of enzymes. It is shown that some current appro
aches, and in particular the empirical valence bond approach, allow us to d
escribe enzymatic reactions by rigorous concepts of current chemical physic
s and to estimate any proposed catalytic contribution. This includes evalua
tion of activation free energies, nonequilibrium solvation, quantum mechani
cal tunneling, entropic effects, and other factors. The ability to evaluate
activation free energies for reactions in water and proteins allows us to
simulate the rate acceleration in enzymatic reactions. It is found that the
most important contribution to catalysis comes from the reduction of the a
ctivation free energy by electrostatic effects. These effects are found to
be associated with the preorganized polar environment of the enzyme active
site. The use of computer simulations as effective tools for examining diff
erent catalytic proposals is illustrated by two examples. First, we conside
r the popular proposal that enzymes catalyze reactions by special dynamical
effects. It is shown that this proposal is not supported by any consistent
simulation study. It is also shown that the interpretation of recent exper
iments as evidence for dynamical contributions to catalysis is unjustified.
Obviously, all chemical reactions involve motion, but unless this motion p
rovides non-Boltzmann probability for reaching the transition state there a
re not dynamical effects. Vibrationally enhanced tunneling is shown to be a
well understood phenomenon that does not lead to special catalytic effects
. Similarly, it is shown that nonequilibrium solvation effects do not const
itute dynamical contributions to catalysis. Second, the effectiveness of si
mulation approaches is also demonstrated in studies of entropic contributio
ns to catalysis. It is found that the corresponding contributions are small
er than previously thought.