DIRECT INTERACTION ENERGY: A COMPUTATIONAL QUANTITY FOR PARAMETERIZATION OF CONDENSED-PHASE FORCE FIELDS AND ITS APPLICATION TO HYDROGEN BONDING
Abstract
Using N-Methylacetamide (NMA) dimer and NMA–water as model complexes, the solvent effect on the protein inter- N–H⋯O=C and intra- N –H⋯OH2, and C=O⋯H2O hydrogen bonding have been studied by the polarizable continuum model (PCM) ab initio calculations in the four media (vacuum, ether, nitromethane and water). In contrast to the empirical approaches, we suggested using the direction interaction energies (DE) to consider the solvent polarization, which can be derived from PCM ab initio calculations. The DEs of the model compounds in solvents are larger than their in vacuo binding energies, which reflect the solvent polarization effect. As the solvents become increasingly polar, the binding free energies decrease while DEs increase. The increasing DE is consistent with the increasing hydrogen bond length. Considering the protein environment, the DEs of NMA-NMA dimer in ether, 9.14 and 9.41 kcal/mol for NMADI and NMADII, are recommended for the intra N–H⋯O=C hydrogen bonding. The DEs of NMA–water complex in water, -5.47 (NMAWI) and -5.41 kcal/mol (NMAWI'), -8.44 (NMAWII) and -8.68 kcal/mol (NMAWII'), respectively, are suggested for the inter- N–H⋯OH2 and C–O⋯H2O hydrogen bonding of proteins. Using the same approach, we have also computed the DE of water dimer in liquid water. The computed DE of water dimer (-5.63 kcal/mol) is larger than the in vacuo water dimerization energy (-5.14 kcal/mol) and in reasonable agreement with the dimerization energies (ranging from –6.0 to 6.8 kcal/mol) of polarization-included empirical water models.
