Improved Parameterization of Amine-Carboxylate and Amine-Phosphate Interactions for Molecular Dynamics Simulations Using the CHARMM and AMBER Force Fields

J Chem Theory Comput. 2016 Jan 12;12(1):430-43. doi: 10.1021/acs.jctc.5b00967. Epub 2015 Dec 16.


Over the past decades, molecular dynamics (MD) simulations of biomolecules have become a mainstream biophysics technique. As the length and time scales amenable to the MD method increase, shortcomings of the empirical force fields, which have been developed and validated using relatively short simulations of small molecules, become apparent. One common artifact is aggregation of water-soluble biomolecules driven by artificially strong charge-charge interactions. Here, we report a systematic atom pair-specific refinement of Lennard-Jones parameters (NBFIX) describing amine-carboxylate and amine-phosphate interactions, which bring MD simulations of basic peptide-mediated nucleic acid assemblies and lipid bilayer membranes into better agreement with experimental data. As our refinement does not affect the existing parametrization of bonded interactions or alter the solvation free energies, it improves the realism of an MD simulation without introducing additional artifacts.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amines / chemistry
  • Amines / metabolism*
  • Carboxylic Acids / chemistry
  • Carboxylic Acids / metabolism*
  • DNA / chemistry
  • DNA / metabolism
  • Lipid Bilayers / chemistry
  • Lipid Bilayers / metabolism*
  • Molecular Dynamics Simulation*
  • Osmotic Pressure
  • Phosphates / chemistry
  • Phosphates / metabolism*


  • Amines
  • Carboxylic Acids
  • Lipid Bilayers
  • Phosphates
  • DNA