FREE-ENERGY OF AMIDE HYDROGEN-BOND FORMATION IN VACUUM, IN WATER, ANDIN LIQUID ALKANE SOLUTION

The energy of dimerization of two N-methylacetamide (NMA) molecules in vacuum is calculated using density functional theory. Natural orbital analysis suggests that the dimerization energy of -6.6 kcal/mol is pr edominantly due to the (N-H ... O=C) donor-acceptor interaction. The g as phase to water hydration free energies and the free energies of tra nsfer from the aqueous phase to liquid alkane of hydrogen bonded, (N-H ... O=C), and nonbonded, (N-H,O=C), groups are calculated using a con tinuum solvent model. On the basis of these calculations, we estimate the free energy of forming an amide hydrogen bond in the context of th e NMA dimer in water and in liquid alkane as similar to-1 and similar to-5 kcal/mol, respectively. The relevance of these calculations to pr ocesses such as protein folding and membrane insertion of proteins is discussed.