Using molecular dynamics simulation to study the polarization response of the liquid water interface to surface charge heterogeneity

The hydration shells of proteins mediate interactions, such as small molecule binding, that are vital to their biological function or in some cases their dysfunction. However, even when the structure of a protein is known, the properties of its hydration environment cannot be easily predicted due to the complex interplay between protein surface heterogeneity and the collective fluctuations of water's hydrogen bonding network. This manuscript presents a theoretical study of the influence of surface charge heterogeneity on the polarization response of the liquid water interface. We introduce a new computational method for analyzing simulation data that is capable of quantifying water's nonlinear polarization response and determining the effective surface charge distribution of hydrated surfaces over atomistic length scales. When applied to a protein, this method is capable of revealing new insight into the influence of conformational dynamics on hydration structure, as we highlight by illustrating how salt-bridge formation enhances the polarization of the local hydration shell. To illustrate the utility of this method, we present the results of molecular dynamics simulations of liquid water in contact with a heterogeneous model surface and the CheY protein.