Computational simulations are a valuable complement to experimental techniques that aim to characterize the changes in protein structure and function that occur upon phosphorylation (or dephosphorylation). This is especially true for IDPs, which exist as an ensemble of structures that may be difficult to deduce from experimental data that often consist of ensemble averages. Molecular dynamics (MD) simulations in particular have been used to study a wide variety of protein properties in general, including protein folding and conformational change. Numerous MD simulations have been performed for various phosphorylated systems in the past, such as tau protein, RNA polymerase III, smooth muscle myosin and others, with the goal to elucidate the conformational changes that phosphoryla-tion introduces to these systems. The accuracy of these simulations, however, is strongly determined by the classical force field used for the MD simulation. Force fields for phosphorylated amino acids have been mainly developed for those relevant for eukaryotes: serine, threonine and tyrosine. These force field parameters are generally available for monoanionic and dianonic protonation states, as these are the relevant forms at physiological pH. In the AMBER force field, phosphorylated amino acid parameters were first created for AMBER ff99 by Homeyer et al. The partial charges were parameterized using RESP, Lennard-Jones parameters were generally taken from phosphodiesters in the AMBER force field, and a variety of new bonded parameters were implemented. Validation was performed in order to ensure that torsional energies reproduced example ab initio calculations. As the Lennard-Jones (LJ) parameters were not optimized for the phosphorylated amino acids, Steinbrecher et al. optimized the oxygen LJ radii on the phosphate group to reproduce solvation free energies computed using thermodynamic cycles, gas phase basicities, and other values from quantum chemistry (QM) calculations of phosphorylated amino acid analogues. There exist another set of force field parameters in AMBER ff03 as part of Forcefield PTM, which was designed for a variety of post-translational modifications, but parameters are only available for the dianionic species of the phosphorylated amino acids in this package. The Amber-Tools 20 distribution includes newly derived side chain torsion parameters have been derived that are compatible with the ff14SB and ff19SB force fields, but the parameterization and validation approaches have not yet been published. Parameters have also been developed for the GROMOS and CHARMM force fields, with parameters either derived from nucleic acids or parameterized similarly to the AMBER force fields. The validation of phosphorylated amino acid parameters by comparing simulation predictions to experiment is lacking in the literature, in contrast to the case of the canonical amino acids. A recent article by Vymětal et al. has pointed out inconsistencies in calculated quantities by the AMBER and CHARMM force fields for the phosphorylated amino acids over a wide range of properties related to their conformational ensembles, such as NMR 3 J couplings, intramolecular hydrogen bonding propensities, conformational preferences, and more; inconsistencies in calculated conformational preferences by AMBER and CHARMM for larger IDPs have also been noted by Rieloff and Skepö . This raises questions about the suitability of current force field parameter sets for simulation of these systems.