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

We compute the stabilization energies of the complexes formed between forma te 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 SI BFA molecular mechanics computations. A very significant amount of cooperat ivity is found by DFT in the formate-(NMF)(n) complexes, amounting to -17 k cal/mol with n = 5, The SIBFA computations with fixed internal geometries f or the monomers recover up to 80% of the DFT values. Singie-point SCF/MP2 c omputations at the SIBFA-optimized geometries give binding energies and coo perativities very close to the SIBFA values. Solvation effects as represent ed by a continuum reaction field procedure are found to affect cooperativit y to a modest extent. The implications for oligopeptides are discussed.