MECHANISM OF HYDRATION OF UREA AND GUANIDIUM ION - A MODEL STUDY OF DENATURATION OF PROTEINS

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.