Fs. Nandel et al., MECHANISM OF HYDRATION OF UREA AND GUANIDIUM ION - A MODEL STUDY OF DENATURATION OF PROTEINS, Pure and applied chemistry, 70(3), 1998, pp. 659-664
The hydration of urea and guanidium ion have been studied by quantum c
hemical and molecular mechanics methods. The hydration of urea takes p
lace only through the amino groups and not through the carbonyl group.
One mole of urea decreases the free concentration of water by seven m
oles and one mole of guanidium ion by twelve moles. The interaction en
ergies (Delta E's) for the hydration of urea and guanidium ion in both
the primary and secondary spheres are more than that of water-water i
nteractions. Also, the interaction energy of urea and guanidium ion wi
th water is more than the interaction energy of urea and guanidium ion
with the potential hydrogen bonding sites in the peptide groups of th
e model pentapeptides. The ''collagen type structure'' (with phi(i)=-3
0 degrees, psi(i)=120 degrees) has been taken as model for functional
domain which is stabilized by interaction with water through free pote
ntial hydrogen bonding sites. It is shown that these denaturants, redu
ce the free concentration/activity of water effectively and remove the
water molecules from the protein surface. The computational results a
lso demonstrate why lower concentrations of guanidium ion is sufficien
t to bring about the denaturation in comparison to urea. The interacti
on studies also reveal that there is no complex formation between the
peptides groups and denaturant molecules. The cause of protein aggrega
tion in the presence of denaturants and hence, the loss of biological
activity is also discussed.