Protein packing defects “heat up” interfacial water

Abstract

Ligands must displace water molecules from their corresponding protein surface binding site during association. Thus, protein binding sites are expected to be surrounded by non-tightly-bound, easily removable water molecules. In turn, the existence of packing defects at protein binding sites has been also established. At such structural motifs, named dehydrons, the protein backbone is exposed to the solvent since the intramolecular interactions are incompletely wrapped by non-polar groups. Hence, dehydrons are sticky since they depend on additional intermolecular wrapping in order to properly protect the structure from water attack. Thus, a picture of protein binding is emerging wherein binding sites should be both dehydrons rich and surrounded by easily removable water. In this work we shall indeed confirm such a link between structure and dynamics by showing the existence of a firm correlation between the degree of underwrapping of the protein chain and the mobility of the corresponding hydration water molecules. In other words, we shall show that protein packing defects promote their local dehydration, thus producing a region of "hot" interfacial water which might be easily removed by a ligand upon association.

Hydrophobicity and geometry: Water at curved graphitic-like surfaces and within model pores in self-assembled monolayers

“…protein binding pockets are expected to be dry or to contain easily removable water which should be displaced by a ligand upon association [9,2,13]. M a n u s c r i p t parallel to the surface, but for graphene the O-H bonds tend to point slightly outerwards, forming an angle close to 70…”

“…In particular, the hydration properties of protein binding sites have been suggested to play a main role in the binding of ligands or in protein-protein association [9,11,13]. From one side, ligands are expected to displace hydration water molecules from their binding site [9,13].…”

“…In particular, the hydration properties of protein binding sites have been suggested to play a main role in the binding of ligands or in protein-protein association [9,11,13]. From one side, ligands are expected to displace hydration water molecules from their binding site [9,13]. On the other hand, geometrically-induced surface dehydration (by means of water inaccessibly cavities) has been shown to be central for the existence of reactive sites responsible for protein binding [11,13].…”

“…From one side, ligands are expected to displace hydration water molecules from their binding site [9,13]. On the other hand, geometrically-induced surface dehydration (by means of water inaccessibly cavities) has been shown to be central for the existence of reactive sites responsible for protein binding [11,13]. In addition, the behavior of water confined in cylindrical pores or tunnels is also important both from the basic and the applied viewpoints.…”

Hydration and Nanoconfined Water: Insights from Computer Simulations

“…However, the picture of (nano) confined water is still far from being complete (Giovambattista et al 2012;Rasaiah et al 2008;Berne et al 2009;Schulz et al 2011;Alarcón et al 2014). This issue is not only crucial from an intrinsic, fundamental level, but also from its far reaching implications (Fernández 2010;Qvist et al 2008;Berne et al 2009;Young et al 2007;Wang et al 2011;Kulp III et al 2011;Accordino et al 2011aAccordino et al , 2012aAccordino et al , b, c, 2013Schulz et al 2011;Sierra et al 2013;Alarcón et al 2014;Bogan and Thorn 1998;Li and Liu 2009). For example, being water the matrix of life, a full understanding of its behavior in the nano and mesoscales would be essential to understand biology at the molecular level.…”