Is protein-protein recognition achieved by evolving hydrogen-bonded chains in interfacial water molecules?

Dhananjay Joshi^1*, Jung-Hsin Lin^1,2,3,4

¹Research Center for Applied Sciences, Academia Sinica, Taipei, 11529, Taiwan
²Institute for Biomedical Sciences, Academia Sinica, Taipei, 11529, Taiwan
³School of Pharmacy, College of Medicine, National Taiwan University, Taipei, 10050, Taiwan
⁴College of Engineering, Chang Gung University, Taoyuan, 33302, Taiwan

* Presenter:Dhananjay Joshi, email:joshid@gate.sinica.edu.tw

It has been an emerging trend to identify the water molecules that play a more explicit role in various recognition process in the cell. The protein-protein recognition mechanism is central and the bulk waters in the interface play an important role. In particular, the role of water molecules in forming a stable protein-protein complex is crucial, especially when the interface is hydrophilic. The dynamic nature of such water molecules on the protein surface is often studied through hydrogen bonding analysis followed by molecular dynamics simulation. Thus far, these interfacial water molecules are analyzed through residence time, occupancy, dipole moment, etc. However, it is still unclear whether the bulk water networks are important in the mechanism of recognition. This study focuses on the water hydrogen-bonded chains formed between the residues that contributes to hydrophilic protein-protein interface. Several subset of hydrogen-bonded water chains are constructed. First, the water molecules between the two protein molecules are trimmed to a smaller cylindrical water tubes, and then the connectivity of the interface residues are analyzed through water hydrogen-bonded chain formation. The connectivity time and residence time of waters in the same chain and across the chains is analyzed. Our studies provide novel insights of how a separated protein interface is dynamically becoming connected through the evolving hydrogen-bonded chains.

Keywords: Protein-protein interactions, Hydrogen bond chains, Molecular dynamics simulation