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>
