  The elucidation of entropic contribution to enzyme catalysis has been debated
over decades. The recent experimentally measured activation enthalpy and
entropy, for chorismate rearrangement reaction in PchB brings up a hotly
debated issue whether the chorismate mutase catalyzed reaction is
entropy-driven reaction. Extensive configurational sampling combined with
quantum mechanics/molecular mechanics molecular dynamics (QM/MM MD) provides an
approach to calculate entropic contribution in condensed phase reactions.
Complete reaction pathway is exploited by QM/MM MD simulations at DFT and
SCC-DFTB levels. The overall entropy change calculated at SCC-DFTB level QM/MM
MD simulations, is close agreement with the experimental value. Conformation
analysis indicates that the self-ordering of chorismate in the active site of
PchB also contributes to total entropy change. This entropy penalty including
conformational transformation entropy and activation entropy cannot be
intuitively speculated from the crystal structure that only acts as a
stationary state along the reaction pathway of PchB catalyzed reaction. This is
the first time to use QM/MM MD simulations to calculate the activation entropy
from the temperature dependence of reliable free energy profiles with extensive
simulation time. The reasonable insight in enthalpy/entropy scheme clarifies
the detailed entropy change and provides a quantitative tool to the
contradicted experimental results.
