By combining simulations with statistical mechanics,
it nevertheless proves possible to study reactions
within the ~100 nanosecond timescale of molecular dynamics.
The central idea in the
reactive flux method
is to express the rate as the product of
i) the probability for a molecule in the reactant state
to reach the transition state, and
ii) the probability of this activated molecule
to proceed to the product state.
The former is calculated by
free energy techniques,
like umbrella sampling or the constraint methods
developed in our group [
1-3].
The second probability follows from relaxation runs
starting at the transition state.
solvent effects
The calculated rates of 36 and 264 per second
for calix[4]arenes in chloroform and benzene, respectively,
are in good agreement with NMR measurements [
4].
The isomerisation of
p-tert-butyl-calix[4]arene,
in which the hydrogens opposite the hydroxyl groups
have been replaced by C(CH3)3,
is considerably more complicated.
With these bulky side groups,
the calix acquires four 'doors' surrounding a central 'cargo bay'.
A solvent molecule or a 'payload' arrested in this cavity
will drastically change the conformational behaviour
[
5].
The free energy methods used here are a recurring theme
in the research of the computational biophysics group.
They are also intensively used in our study of
pores in lipid membranes.
![A calix[4]arene in the partial cone (paco) conformation](reaction.gif)