Contiguous Patches of Translational Hydration Dynamics on the Surface of K-Ras

TL;DR

This study uses ODNP to analyze hydration dynamics on K-Ras protein surfaces, revealing uniform water translational mobility across regions, which could inform understanding of protein-ligand interactions.

Contribution

It demonstrates that water dynamics are consistent across nearby residues on K-Ras, enabling comprehensive hydration mapping at nanometer scales.

Findings

Water mobility is similar across regions of K-Ras surface.

Hydration dynamics are uniform within nanometer-scale regions.

Potential to map hydration layers to understand binding energetics.

Abstract

Proteins involved in signaling pathways represent an interesting target for experimental analysis by ODNP (Overhauser Dynamic Nuclear Polarization), which determines the translational mobility at the surface of proteins. They also represent a challenge, since the hydration dynamics at all sites remains relatively rapid, requiring sensitive measurements capable of drawing finer distinctions. Targeting the protein K-Ras, we find ODNP cross-relaxivity values that appear consistent within similar regions of 3D space, regardless of the specific residue where the spin probe used to select the location has been attached. The similar dynamics observed from nearby residues indicate a persistence/uniformity of the translational dynamics of water on the nanometer scale. This results makes sense, since it essentially means that the dynamics of water remains consistent over a lengthscale (a nanometer) over which liquid water exhibits structural persistence (i.e. its correlation length). This opens up the possibility of strategically and comprehensively mapping out the hydration layer in aqueous solution and identifying regions that contribute significantly to the free energy of binding interactions -- for example, slow water that might contribute significant entropy, or regions with strongly temperature-dependent water mobility that might contribute significant enthalpy.