A Kirkwood‐Buff derived force field for amides

Abstract

A force field for the computer simulation of aqueous solutions of amides is presented. The force field is designed to reproduce the experimentally observed density and Kirkwood-Buff integrals for N-methylacetamide (NMA), allowing for an accurate description of the NMA activity. Other properties such as the translational diffusion constant and heat of mixing are also well reproduced. The force field is then extended to include N,N'-dimethylacetamide and acetamide with good success. Analysis of the simulations of low concentrations of NMA in water indicates a high degree of solvation with only 15% of the NMA molecules involved in solute-solute hydrogen bonding. There is only a weak angular dependence of the solute-solute hydrogen bonding interaction with a minimum at an angle of 65 degrees for the N-H and C=O dipole vectors. The models presented here provide a basis for an accurate force field for peptides and proteins.