title: Adhesive water networks facilitate binding of protein interfaces.
abstract: Water structure has an essential role in biological assembly. Hydrophobic dewetting has been documented as a general mechanism for the assembly of hydrophobic surfaces; however, the association mechanism of hydrophilic interfaces remains mysterious and cannot be explained by simple continuum water models that ignore the solvent structure. Here we study the association of two hydrophilic proteins using unbiased extensive molecular dynamics simulations that reproducibly recovered the native bound complex. The water in the interfacial gap forms an adhesive hydrogen-bond network between the interfaces stabilizing early intermediates before native contacts are formed. Furthermore, the interfacial gap solvent showed a reduced dielectric shielding up to distances of few nanometres during the diffusive phase. The interfacial gap solvent generates an anisotropic dielectric shielding with a strongly preferred directionality for the electrostatic interactions along the association direction.
authors: Center for Bioinformatics, Saarland University, Building E 2.1, Postfach 15 11 50, Saarbruecken 66041, Germany.
authors: Mazen
authors: M
authors: Ahmad
authors: Wei
authors: W
authors: Gu
authors: Tihamér
authors: T
authors: Geyer
authors: Volkhard
authors: V
authors: Helms
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry*; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D056004:Molecular Dynamics Simulation; D054730:Protein Interaction Domains and Motifs; D017434:Protein Structure, Tertiary; D012260:Ribonucleases / Q000737:chemistry*; D014867:Water / Q000737:chemistry*
chemical_list: D001426:Bacterial Proteins; D014867:Water; C057438:barstar protein, Bacillus amyloliquefaciens; D012260:Ribonucleases; C019760:Bacillus amyloliquefaciens ribonuclease