The first conference focusing exclusively on the relation between enzyme dynamics and catalysis took place in Mesilla, New Mexico, in February 2000. Six years later, what looked controversial then has become widely accepted. The basic enzymatic catalysis mechanisms, transition state binding1 and ground-state destabilization, 2 are still accepted. What changed is a willingness to admit the possibility that motions of residues near the active site can have an effect on the catalytic mechanism and that should be taken into account in the interpretation of, for example, kinetic isotope effect (KIE) measurements.

These motions can influence the standard model of catalysis in different ways, presented in order of increasing controversy:(1) they may be extended motions related to conformational fluctuations;(2) they may be local subpicosecond motions near the active site;(3) they may force us to revise3 our view of thermodynamic cycles often used to describe catalysis. 4