The Protein Force Field Plays a Crucial Role in Obtaining Accurate Macromolecular Ensembles of IDPs

Atomistic models of water with increased dispersion interactions (e.g., OPC, TIP4P-D) have been proposed to produce extended conformational ensembles of intrinsically disordered proteins (IDPs). However, the role of the protein force field in obtaining accurate macromolecular ensembles of IDPs remains unclear. Isolating the influence of the protein and water models by comparison to an experimental measure (such as X-ray scattering) requires an atomic consideration of the hydration layer waters around a thermally fluctuating protein. To enable an atomically detailed scattering calculation around a thermally fluctuating solute, we have developed a new scattering model termed small and wide angle X-ray scattering for all molecular dynamics engines (SWAXS-AMDE). SWAXS-AMDE can handle the trajectory files from all of the popular molecular dynamics (MD) simulation softwares, thus facilitating a straightforward validation of force field improvements. SWAXS-AMDE computed scattering profiles for polyampholyte peptides show the AMBER ff19SB protein force field to play a crucial role in obtaining accurate macromolecular ensembles of both folded proteins and IDPs.