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Dehydron

synthesis of a multiscale theory of biological water


The dehydron is a concept pertaining to the field of epistructural biology. A dehydron may be identified as a type of solvent-exposed intramolecular backbone hydrogen bond in a soluble protein. Dehydrons were originally characterized as structural defects or vulnerabilities of proteins by Ariel Fernandez and collaborators Ridgway Scott and Harold Scheraga. Dehydrons are promoters of their own dehydration since the removal of episteric water enhances the stability and strength of the underlying electrostatic interaction. Dehydrons represent structural defects since the exposure of the protein to backbone hydration may lead to structural disruption.  The mechanical equivalent of the dehydration propensity of a dehydron has been named dehydronic force by Ariel Fernandez and has been measured as the attractive drag exerted by the dehydron on a test nonpolar group such as a methane molecule. The dehydronic field is orthogonal to the Colombic field defined by the partial charges on the dehydron-paired polar groups. Dehydrons are at the heart of a multiscale theory of biological water introduced by Ariel Fernandez: they create interfacial tension in soluble proteins because the water molecules interacting with the paired amide and carbonyl relinquish some level of coordination relative to bulk solvent. This interfacial tension has been computed by Ariel Fernandez in 2011-2014 along with a comprehensive thermodynamic treatment of interfacial biological water that yielded the concept of nanofugacity and a variational treatment of interfacial water mechanics. 

As demonstrated by Ariel Fernandez and collaborators, dehydrons are utilized by evolution as a molecular dimension to foster complexity while retaining the same molecular machinery for biological function, albeit making it more allosteric and cooperative in species with low effective population.

Since dehydron patterns are typically not conserved across homologous proteins in humans, they may be targeted by drugs/ligands capable of contributing to their dehydration upon association with the target protein. This tenet is the foundation of the drug-selectivity filter discovered by the Ariel Fernandez's group at Rice University and has lead to the so-called wrapping technology in drug discovery.

The biophysical apparatus and biomedical applications of dehydron theory are comprehensively described in the book "Transformative Concepts for Drug Design: Target Wrapping", Author: Ariel Fernandez, Springer,-Verlag, Berlin (2010).