Modeling protein-protein interactions through alanine-amide hydrogen bonds

The hydrogen-bonded complexes formed between alanine and formamide and between alanine and N-methylformamide have been completely investigated in the present study using ab initio molecular orbital theory (MP2) and density functional theory (B3LYP) using aug-cc-pVDZ basis set. Geometry optimization and vibrational frequency calculations have been carried out for isolated and hydrogen-bonded systems. The stabilization energies (∆EBSSE) suggest that alanine-N-methylformamide complexes are more stable than alanine-formamide complexes. The tendency of N-H of amide to act as hydrogen bond (HB) donor is found to be much better in relative to the N-H of amino group of alanine. The study suggests that the tendency of carbonyl oxygen of amide to act as HB acceptor towards various sites of alanine decreases in the order O–H > N–H > C–H. The results are corroborated by natural bond orbital (NBO) analysis, Bader’s theory of atoms in molecules (AIM) and molecular electrostatic potential (MEP) studies. The blue and red shifts in the stretching frequencies of HB donors X-H (X = O, N, C) have also been analysed.