The EVB as a quantitative tool for formulating simulations and analyzing biological and chemical reactions.

Recent years have seen dramatic improvements in computer power, allowing ever more challenging problems to be approached. In light of this, it is imperative to have a quantitative model for examining chemical reactivity, both in the condensed phase and in solution, as well as to accurately quantify physical organic chemistry (particularly as experimental approaches can often be inconclusive). Similarly, computational approaches allow for great progress in studying enzyme catalysis, as they allow for the separation of the relevant energy contributions to catalysis. Due to the complexity of the problems that need addressing, there is a need for an approach that can combine reliability with an ability to capture complex systems in order to resolve long-standing controversies in a unique way. Herein, we will demonstrate that the empirical valence bond (EVB) approach provides a powerful way to connect the classical concepts of physical organic chemistry to the actual energies of enzymatic reactions by means of computation. Additionally, we will discuss the proliferation of this approach, as well as attempts to capture its basic chemistry and repackage it under different names. We believe that the EVB approach is the most powerful tool that is currently available for studies of chemical processes in the condensed phase in general and enzymes in particular, particularly when trying to explore the different proposals about the origin of the catalytic power of enzymes.