sentences:  Often such theoretical effective concentrations are unphysical and impossible to realize in reality - which is a testament to the great catalytic power of many enzymes, with massive rate increases over the uncatalyzed state.However, the situation might be more complex, since modern computational studies have established that traditional examples of proximity effects cannot be related directly to enzyme entropic effects.Also, the original entropic proposal has been found to largely overestimate the contribution of orientation entropy to catalysis.