Discrete Solvent Effects Around Dehydrons

Both order and native disorder are well-characterized structural attributes of protein chains [16]. However, the highly vulnerable regions in a soluble fold described in this chapter belong to the novel category of tamed disorder because they can acquire and maintain a structured state only upon association. Neither order nor disorder is an adequate category to describe such dehydron-rich protein regions. 

These discrete effects relating to local water structuring around packing defects cannot be captured properly by existing continuous models of the interfacial electrostatics [17]. This is mainly because such models are based on mean-force potential approximations to solvent interactions, where solvent degrees of freedom are averaged out, and this is clearly an inappropriate ansatz to deal with cavities of the size of solvent molecules themselves. 

The thermal average, T , of the number of hydrogen bond partnerships involving water molecules hydrating the p53 DNA-binding domain was obtained from 

5 Under-Wrapped Proteins in the Order-Disorder Twilight 

This computation was repeated to include representatives of the three major fold topologies all-P (SH3 domain, N = 55, 2 dehydrons, PDB.1SRL), all-a (X-repressor, N = 86, 26 dehydrons, PDB.1LMB), and a/fi (ubiquitin, N = 76, 16 dehydrons, PDB.1UBI). Consistency with the p53 calculation was obtained, as dehydrons proved to become the dehydration hot spots on the protein interface [19]. 

---