Ok, here's my big question.
I've just been reading Arieh Warshel's "Computer Modelling of Chemical
Reactions in Enzymes and Solutions" and the last chapter really got me
interested (Chpt 9 "How Do Enzymes Really Work").
Here Warshel puts forward the question "how does an enzyme accomplish the
stabilisation of a transition-state relative to the reaction in water?"
He examines the main options, the strain hypothesis, desolvation, dynamic
fluctations, entropic factors and electrostatics.
Strain Hypothesis: The steric force of the enzyme active-site reduces the
activation energy by destabilising the ground state.
Desolvation Hypothesis: The active-site desolvates the ground state and so
reduces the energy barrier associated with the transition state.
Dynamic Fluctuations: An enzyme may utilise special fluctuations not
available for the corresponsding reaction in solution.
Entropic Factors: Often expressed differently, but essentially the ground
state free energy is raised by fixing reactants (and products) in an exact
(preferred?) orientation and this becomes a major catalytic effect.
Electrostatic Energy: Mentioned last, this was always going to be put
forward as the big "thing". Electrostatic stabilisation of the transition
state by the surrounding active-site, and here's where it gets very
interesting but I would have liked stronger language - "apparently",
enzymes can create microenvironments which compliment by their
electrostatic potential the *changes* in charges during the corresponding
reactions. Thus you have a simple and effective way of reducing the
activation energies in enzymatic reactions.
Any comments? Agreement or perhaps it's more of a "rich tapestry". The
last one seems interesting in terms of MCA. Could a whole pathway be
viewed as such a microenvironment?
Len...
