Adhesive Water Networks Facilitate Binding Of Hydrophilic Protein Interfaces

It is well known that bulk water plays a crucial role in the biological assembly of hydrophilic surfaces. In this work, we emphasize the special molecular nature of bridging water networks in the formation of biomolecular contacts driven by electrostatic interactions. We have studied the assembly of two hydrophilic protein interfaces. Extensive atomistic molecular dynamics simulations reproducably recovered the native bound state of the Barnase:Barstar complex as seen in the crystal structure of the complex and thus give atomistic insight into the mechanism of binding. The simulations showed the structured water in the interfacial gap to play an adhesive role between the interfaces by forming a strong hydrogen bond network between the interfaces with a reduced dielectric constant compared to bulk. The role of this network is relevant already during the diffusive phase and stabilizes the early intermediate states before native contacts are formed. The convergence to the stereo-specific complex was accompanied by maximizing the interfacial water-mediation and formation of the highly hydrated stereo-specific complex. We introduce a new graph-based methodology to quantify the connectness of water networks.