(563b) Sequence Modulates Polypeptoid Hydration Water Structure and Dynamics

Polypeptoids have become an important class of polymers, capable of precisely defined sequences while remaining gram-synthesizable—properties that have driven a rapidly expanding set of applications and also make polypeptoids ideal model heteropolymers for insight into sequence-structure-function relationships. However, such relationships have been challenging to establish for structurally disordered polypeptoids, which adopt a wide range of conformations in solution and are thus difficult to characterize. Here, we first present a computational workflow to characterize the conformational landscape of disordered polypeptoids using enhanced-sampling molecular dynamics. We validate this workflow using experimental measurements of the full end-to-end distance distributions from Double Electron-Electron Resonance (DEER) spectroscopy, which show excellent agreement with the simulations. We then leverage the workflow to probe shifts in polypeptoid hydration behavior with sequence, which is central to many key polypeptoid applications, such as antifouling coatings. We show that water near polypeptoids with hydrophobic monomers is less dense, more tetrahedral, and slower than water near polypeptoids with hydrophilic monomers. This effect is independent of sequence-induced changes in polypeptoid conformation, suggesting that changes in chemistry alone are sufficient to induce shifts in water structure and dynamics at molecular scales. Furthermore, these shifts in water structure and dynamics are correlated, indicating that experimental probes of local water dynamics may also indirectly provide insight into structural shifts.