(410h) Explicit Water Molecular Dynamics Is Indispensable for Validating Simulated Scattering Profiles of Polyampholytes Against SAXS

Polyampholytes are polymers that contain both positively and negatively ionizable groups. They are low complexity sequences and serve as building blocks in understanding the solution behavior of intrinsically disordered proteins. The precision-tailoring of polyampholyte sequences and their
subsequent investigation of solution properties using small angle X-ray scattering (SAXS) presents a compelling opportunity to validate the theories and simulation models of this class of materials. Simulations of polyampholytes have usually relied on either describing the solvent implicitly or coarse-graining the polyampholyte itself. Such methods are of limited utility in describing hydration and in generating accurate structural ensembles. Further, due to their inability in describing the density variation of solvent around the solute, implicit solvent methods also rule out a one-to-one comparison of scattering profiles with SAXS. In our study, we simulated five different polyampholyte sequences in explicit solvent. Using the information contained in the simulation trajectories, different techniques for describing the hydration layer and computing scattering profiles were compared. For better comparison with SAXS and the experimentally inferred radii of gyration, we find that it is essential to account for water molecules that are strongly associated with the polymapholyte. Overall, our results show that accounting for the molecular nature of the solvent is indispensable in interpreting results from SAXS meaurements.