Electronic structure theory, which in recent years has been actively and ef
fectively applied to the modeling of chemical reactions involving transitio
n-metal complexes, is now also being applied to the modeling of biological
processes involving metalloenzymes. In the first part of this paper, we rev
iew our recent electronic structure studies using relatively simple models
of two metalloenzymes - methane monooxygenase and ribonucleotide reductase.
In the second part of the paper, we review a new hybrid theoretical method
we have developed for modeling the reactivities of large molecular systems
. We describe the limitations of these models and indicate how they may be
further improved to reliably model the reactivities of complicated metalloe
nzymes.