Many-body effects in systems of peptide hydrogen-bonded networks and their contributions to ligand binding: A comparison of the performances of DFT and polarizable molecular mechanics

We compute the stabilization energies of the complexes formed between formate or water and a linear array of n = 2-5 N-methylformamide (NMF) molecules. We perform density functional theory (DFT), ab initio SCF and MP2, and SIBFA molecular mechanics computations. A very significant amount of cooperativity is found by DFT in the formate-(NMF)(n) complexes, amounting to -17 kcal/mol with n = 5, The SIBFA computations with fixed internal geometries for the monomers recover up to 80% of the DFT values. Singie-point SCF/MP2 computations at the SIBFA-optimized geometries give binding energies and cooperativities very close to the SIBFA values. Solvation effects as represented by a continuum reaction field procedure are found to affect cooperativity to a modest extent. The implications for oligopeptides are discussed.