Nc. Singha et al., ON THE RELATIONSHIP OF THERMODYNAMIC PARAMETERS WITH THE BURIED SURFACE-AREA IN PROTEIN-LIGAND COMPLEX-FORMATION, Bioscience reports, 16(1), 1996, pp. 1-10
Prediction of thermodynamic parameters of protein-protein and antigen-
antibody complex formation from high resolution structural parameters
has recently received much attention, since an understanding of the co
ntributions of different fundamental processes like hydrophobic intera
ctions, hydrogen bonding, salt bridge formation, solvent reorganizatio
n etc. to the overall thermodynamic parameters and their relations wit
h the structural parameters would lead to rational drug design. Using
the results of the dissolution of hydrocarbons and other model compoun
ds the changes in heat capacity (PC,), enthalpy (Delta H) and entropy
(Delta S) have been empirically correlated with the polar and apolar s
urface areas buried during the process of protein folding/unfolding an
d protein-ligand complex formation. In this regard, the polar and apol
ar surfaces removed from the solvent in a protein-ligand complex have
been calculated from the experimentally observed values of changes in
heat capacity (Delta C-p) and enthalpy (Delta H) for protein-ligand co
mplexes for which accurate thermodynamic and high resolution structura
l data are available, and the results have been compared with the x-ra
y crystallographic observations. Analyses of the available results sho
w poor correlation between the thermodynamic and structural parameters
. Probable reasons for this discrepancy are mostly related with the re
organization of water accompanying the reaction which is indeed proven
by the analyses of the energetics of the binding of the wheat germ ag
glutinin to oligosaccharides.