Condensed-phase properties of n-alkyl-amines from molecular dynamics simulations using charge equilibration force fields

Charge equilibration force fields are applied to molecular dynamics simulations of liquid straight-chain alkyl-amine systems-methylamine, ethylamine, and n-propylamine. The models used are based on the CHARMM charge equilibration force field developed for methylamine and applied here to simulations for larger n-alkyl amines. The effects of the parameter set used for extension to larger systems, and the importance of defining the extent of molecular charge transfer via judicious selection of charge normalization units are considered and evaluated. Condensed-phase properties including molecular volumes. enthalpy of vaporization, isothermal compressibility, isobaric heat capacity, dielectric constants, and self-diffusion constants are calculated for each system. Molecular volumes are predicted to within 2.3-18.0% of the experimental values, where the error increases with the size of the molecule. Enthalpy of vaporization is predicted to be within 2.5-24.4% of experiment. Dielectric constants are calculated within 0.5-17.3% of experimental values. Properties of ethylamine and n-propylamine (to which the original charge equilibration force field was not calibrated/fitted) calculated using parameters from an alkane model outperformed those from a lysine model in most cases by up to a 16% reduction in error from experiment. Compared to previous MD simulations [T. Kosztolanyi, I. Bako, and G. Palinkas, Hydrogen Bonding in Liquid Methanol, Methylamine, and Methanethiol Studied by Molecular-Dynamics Simulations. journal of Chemical Physics, 2003. 118(10): 4546-4555.], the radial distribution functions (RDF) of methylamine showed reduced values of the first maximum and minimum position by up to 8.2% for N-N and 12.4% for N-H. The need for careful treatment of charge transfer schemes is suggested by the significant difference in condensed-phase and single-molecule properties when charge transfer was normalized in a partitioned n-propylamine molecule as opposed to normalization over the whole molecule. The partitioned normalization reduced the error from experiment nearly 15% for molecular volume and 10% for enthalpy of vaporization. The influence of various applied normalization schemes on condensed-phase and select gas-phase properties (gas-phase dipole moment) was greater than the effects of different parameterizations. indicating the importance of a proper selection of charge normalization unit in the application and parameterization of charge equilibration force fields for small molecules to larger biological assemblies. (C) 2008 Elsevier B.V. All rights reserved.