Hi All thanks for your detailed reply. A higher RMSF(as I showed in the png.) *doesnot *mean that the RMSD for Calpha backbone showed be high. Am I correct ?? Because in my case the backbone RMSD for the receptor of the peptide bound structure is lower than the receptor alone. Because I wanted to know if my simulations have gone fine. thanks again in advance. Anita
On Sun, Dec 9, 2012 at 6:44 PM, Chandra Verma <chan...@bii.a-star.edu.sg>wrote: > 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 > <jt...@tsurumi.yokohama-cu.ac.**JP<jt...@tsurumi.yokohama-cu.ac.jp> > >: > > 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> >>> >>
