Sequence modulates polypeptoid hydration water structure and dynamics - GAP 1

Research Details

  • Molecular dynamics simulations show that water is less dense, more tetrahedral, and slower near a peptoid compared to bulk. These effects are enhanced with increasing number of polar residues.
  • Shifts in water tetrahedrality near the peptoids are strongly correlated with shifts in water’s translational and rotational dynamics.


This work uncovers relationships between polypeptoid sequence and its hydration water structure and dynamics in dilute solution. Insight into water’s response to chemically and topologically heterogeneous surfaces, and especially dynamic, disordered molecules such as polypeptoids, is key to ultimately tuning that response. Molecular dynamics simulations provide nanoscopic insight into water's structure and dynamics. We had previously developed and validated a computational workflow for simulating long, disordered polypeptoids, which we then applied here to simulate a series of polypeptoids with varying number and placement of polar and nonpolar residues.

We showed that polypeptoid hydration water exhibits fundamentally different behavior compared to the hydration water of structured, extended surfaces. Specifically, replacing polar groups along the polypeptoid backbone with nonpolar groups enhances the hydration water’s tetrahedrality (red markers in the figure) and reduces its dynamics (black markers). A possible explanation for the distinct behavior of these dynamic molecules is that changes in sequence induce shifts in the conformational distribution, which alters the molecular topology that hydration water experiences. The inability to separate out these conformational effects has hindered previous studies of disordered molecules. However, comparing hydration water behavior of common sets of conformations over different sequences reveals that polypeptoid sequence influences water structure and dynamics, even when controlling for the effect of conformation. Remarkably, water structure and water dynamics are correlated in the hydration shell, importantly suggesting that experiments probing local water dynamics may also provide insight into water structure. We furthermore demonstrated the ability of an experimental technique, Overhauser Dynamic Nuclear Polarization, to probe these kinds of site-specific dynamics. This study resolved key questions regarding the effect of chemically heterogeneous molecular surfaces on water behavior, and our consequent ability to control such behaviors via molecular patterning.


This work was supported by the Center for Materials for Water and Energy Systems (M-WET), an Energy Frontier Research Center funded by the U.S. Department of Energy, Office of Science, Basic Energy Sciences under Award #DE-SC0019272. Use was made of computational facilities purchased with funds from the National Science Foundation (OAC-1925717) and administered by the Center for Scientific Computing (CSC). The CSC is supported by the California NanoSystems Institute and the Materials Research Science and Engineering Center (MRSEC; NSF DMR 1720256) at UC Santa Barbara. We acknowledge use of MRL Shared Experimental Facilities, which are also supported by the MRSEC Program of the NSF under Award No. DMR 1720256; a member of the NSF-funded Materials Research Facilities Network ( Support for the ODNP studies was provided by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy─EXC-2033─Project number 390677874. S.J. acknowledges support by the National Science Foundation Graduate Research Fellowship (DGE 1650114). D.R.M. acknowledges support from the MRSEC Program of the National Science Foundation under Award No. DMR 1720256. A.D. acknowledges support by the National Defense Science & Engineering Graduate (NDSEG) Fellowship Program.

Related publication

Sally Jiao, Daniela M. Rivera Mirabal, Audra J. DeStefano, Rachel A. Segalman, Songi Han, and M. Scott Shell, "Sequence Modulates Polypeptoid Hydration Water Structure and Dynamics," Biomacromolecules, 23(4), 1745-1756, 2022 March 11,