to complement the very nice description by jeremy, you may wish to try
and decompose the vibrational modes to get this sense by focussing on
the origins of the "red shift" in the vibrational spectrum and this
accounts largely for the increased vibrational entropies upon
complexation. This paper may be used as a guide
(Dissecting the vibrational entropy change on protein/ligand binding:
burial of a water molecule in bovine pancreatic trypsin inhibitor J
Phys Chem B 2001 105 8050-8055)
&
There is some very nice work by Olano & Rick in
JACS 2004 126:7991 on Hydration free energies and entropies for water
in protein interiors.
and by carol post on how the increased entropies upon complexation are
the origin of the mechanism of some drugs. (for example Influence of
an Antiviral Compound on the Temperature Dependence of Viral Protein
Flexibility and Packing: a Molecular Dynamics Study J. Mol. Biol.
(1998) 276: 331-337)
Quoting Jeremy Tame <[email protected]>:
Different proteins do different things. Some adopt fewer
conformations and a more rigid structure after binding
a ligand, and others do the opposite. Haemoglobin is a nice example
of a protein that becomes a lot more flexible
after picking up ligands. For any reaction of the kind P + L -> PL
there is an entropy cost of making one molecule
from two. For the protein to activate low frequency modes in the
complex is one way to compensate for this by
increasing the entropy of the bound form. The paper by Sturtevant
(PNAS 74, 2236, 1977) is worth a read, as is
Cooper and Dryden (Eur Biophys J, 11, 103, 1984), if you are
interested in relating fluctuations to thermodynamics.
All too often people attempt direct comparisons of structural models
and affinities without realising that the so-called
"angstroms to calories" problem often frames the question in a form
that cannot be answered sensibly. For
example, imagine a protease which is produced as a zymogen. Both
forms may have essentially identical crystal
structures even though the zymogen is more flexible. The protease
can be activated by loss of vibrational modes
in the unbound state which are re-awakened in the complex with
substrate; hence the zymogen will have lower
substrate binding and activity. You might be interested in a review
by Homans (ChemBioChem 6, 1585, 2005) which
discusses the use of NMR to look at entropy changes in
protein-ligand binding reactions. It is by no means unusual
for a residue's entropy to increase in the bound state, although in
your case it seems to be the whole protein!
On Dec 9, 2012, at 1:05 PM, anita p wrote:
Hi All,
I am trying to understand the mechanism of protein-peptide
interaction in two complexes (protein-pepA and protein-pepB).
While trying to perform some simulation experiments, I find that
the root mean square fluctuation (RMSF) by residues of protein in
the complex is higher than that of the protein alone.
Please refer the figure attached to this email. pepA binds with
higher affinity (in uM-range) than pepB according to invitro studies.
Does this happen normally?? Please advice.
Thanks in advance
Anita
<RMSF.png>
