Force field parameters for the simulation of modified histone tails

We describe the development of force field parameters for methylated lysines and arginines, and acetylated lysine for the CHARMM all-atom force field. We also describe a CHARMM united-atom force field for modified sidechains suitable for use with fragment-based docking methods. The development of these parameters is based on results of ab initio quantum mechanics calculations of model compounds with subsequent refinement and validation by molecular mechanics and molecular dynamics simulations. The united-atom parameters are tested by fragment docking to target proteins using the MCSS procedure. The all-atom force field is validated by molecular dynamics simulations of multiple experimental structures. In both sets of calculations, the computational predictions using the force field were compared to the corresponding experimental structures. We show that the parameters yield an accurate reproduction of experimental structures. Together with the existing CHARMM force field, these parameters will enable the general modeling of post-translational modifications of histone tails.