J.
Phys. Chem. B 105,
8050-8055 (2001).
Dissecting
the vibrational entropy change on protein/ligand binding : burial of a
water molecule in bovine pancreatic trypsin inhibitor.
Stefan Fischer, Jeremy
C. Smith, Chandra S. Verma
Abstract
Using
normal mode analysis, the vibrational entropy change on burial of a crystallographically
well-ordered water molecule in the Bovine Pancreatic Trypsin Inhibitor
(BPTI) is dissected.The vibrational
entropy content of the complex is 13.4 cal/mol/K higher than that of the
unbound protein. A detailed analysis is performed of how the translational
and rotational degrees of freedom of the isolated water molecule are transformed
into vibrationalmodes in the complex.This
process is shown to be well described by a model of the complex in which
the water molecule librates in a rigid protein cage. These librational
modes contribute 9.4 cal/mol/K to the entropy change. The remaining 4 cal/mol/K
arises from increased protein flexibility due to softening of the delocalized
modes, mostly in the frequency range below 50 cm-1.The
dominant librational entropy effect suggests a method by which an estimation
of the vibrational contribution to ligand binding can be efficiently computed.